Below you will find scientific publications authored by our members or those enabled by our platform services.
2008
Pan, You Fu; Wansa, K D Senali Abayratna; Liu, Mei Hui; Zhao, Bing; Hong, Shu Zhen; Tan, Peck Yean; Lim, Kar Sian; Bourque, Guillaume; Liu, Edison T; Cheung, Edwin
Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements Journal Article
In: J Biol Chem, vol. 283, no. 47, pp. 32977–32988, 2008, ISSN: 0021-9258.
Abstract | Links | BibTeX | Tags:
@article{pmid18728018b,
title = {Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements},
author = {You Fu Pan and K D Senali Abayratna Wansa and Mei Hui Liu and Bing Zhao and Shu Zhen Hong and Peck Yean Tan and Kar Sian Lim and Guillaume Bourque and Edison T Liu and Edwin Cheung},
doi = {10.1074/jbc.M802024200},
issn = {0021-9258},
year = {2008},
date = {2008-11-01},
journal = {J Biol Chem},
volume = {283},
number = {47},
pages = {32977--32988},
abstract = {Nuclear signaling by estrogens rapidly induces the global recruitment of estrogen receptors (ERs) to thousands of highly specific locations in the genome. Here, we have examined whether ER binding sites that are located distal from the transcription start sites of estrogen target genes are functionally relevant. Similar to ER binding sites near the proximal promoter region, ER binding sites located at distal locations are occupied by ERs after estrogen stimulation. And, like proximal bound ERs, ERs occupied at distal sites can recruit coactivators and the RNA polymerase transcription machinery and mediate specific structural changes to chromatin. Furthermore, ERs occupied at the distal sites are capable of communicating with ERs bound at the promoter region, possibly via long range chromosome looping. In functional analysis, disruption of the response elements in the distal ER binding sites abrogated ER binding and significantly reduced transcriptional response. Finally, sequence comparison of the response elements at the distal sites suggests a high level of conservation across different species. Together, our data indicate that distal ER binding sites are bona fide transcriptional enhancers that are involved in long range chromosomal interaction, transcription complex formation, and distinct structural modifications of chromatin across large genomic spans.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bourque, Guillaume; Leong, Bernard; Vega, Vinsensius B; Chen, Xi; Lee, Yen Ling; Srinivasan, Kandhadayar G; Chew, Joon-Lin; Ruan, Yijun; Wei, Chia-Lin; Ng, Huck Hui; Liu, Edison T
Evolution of the mammalian transcription factor binding repertoire via transposable elements Journal Article
In: Genome Res, vol. 18, no. 11, pp. 1752–1762, 2008, ISSN: 1088-9051.
Abstract | Links | BibTeX | Tags:
@article{pmid18682548b,
title = {Evolution of the mammalian transcription factor binding repertoire via transposable elements},
author = {Guillaume Bourque and Bernard Leong and Vinsensius B Vega and Xi Chen and Yen Ling Lee and Kandhadayar G Srinivasan and Joon-Lin Chew and Yijun Ruan and Chia-Lin Wei and Huck Hui Ng and Edison T Liu},
doi = {10.1101/gr.080663.108},
issn = {1088-9051},
year = {2008},
date = {2008-11-01},
journal = {Genome Res},
volume = {18},
number = {11},
pages = {1752--1762},
abstract = {Identification of lineage-specific innovations in genomic control elements is critical for understanding transcriptional regulatory networks and phenotypic heterogeneity. We analyzed, from an evolutionary perspective, the binding regions of seven mammalian transcription factors (ESR1, TP53, MYC, RELA, POU5F1, SOX2, and CTCF) identified on a genome-wide scale by different chromatin immunoprecipitation approaches and found that only a minority of sites appear to be conserved at the sequence level. Instead, we uncovered a pervasive association with genomic repeats by showing that a large fraction of the bona fide binding sites for five of the seven transcription factors (ESR1, TP53, POU5F1, SOX2, and CTCF) are embedded in distinctive families of transposable elements. Using the age of the repeats, we established that these repeat-associated binding sites (RABS) have been associated with significant regulatory expansions throughout the mammalian phylogeny. We validated the functional significance of these RABS by showing that they are over-represented in proximity of regulated genes and that the binding motifs within these repeats have undergone evolutionary selection. Our results demonstrate that transcriptional regulatory networks are highly dynamic in eukaryotic genomes and that transposable elements play an important role in expanding the repertoire of binding sites.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chen, Xi; Xu, Han; Yuan, Ping; Fang, Fang; Huss, Mikael; Vega, Vinsensius B; Wong, Eleanor; Orlov, Yuriy L; Zhang, Weiwei; Jiang, Jianming; Loh, Yuin-Han; Yeo, Hock Chuan; Yeo, Zhen Xuan; Narang, Vipin; Govindarajan, Kunde Ramamoorthy; Leong, Bernard; Shahab, Atif; Ruan, Yijun; Bourque, Guillaume; Sung, Wing-Kin; Clarke, Neil D; Wei, Chia-Lin; Ng, Huck-Hui
Integration of external signaling pathways with the core transcriptional network in embryonic stem cells Journal Article
In: Cell, vol. 133, no. 6, pp. 1106–1117, 2008, ISSN: 1097-4172.
Abstract | Links | BibTeX | Tags:
@article{pmid18555785b,
title = {Integration of external signaling pathways with the core transcriptional network in embryonic stem cells},
author = {Xi Chen and Han Xu and Ping Yuan and Fang Fang and Mikael Huss and Vinsensius B Vega and Eleanor Wong and Yuriy L Orlov and Weiwei Zhang and Jianming Jiang and Yuin-Han Loh and Hock Chuan Yeo and Zhen Xuan Yeo and Vipin Narang and Kunde Ramamoorthy Govindarajan and Bernard Leong and Atif Shahab and Yijun Ruan and Guillaume Bourque and Wing-Kin Sung and Neil D Clarke and Chia-Lin Wei and Huck-Hui Ng},
doi = {10.1016/j.cell.2008.04.043},
issn = {1097-4172},
year = {2008},
date = {2008-06-01},
journal = {Cell},
volume = {133},
number = {6},
pages = {1106--1117},
abstract = {Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lin, Chi Ho; Bourque, Guillaume; Tan, Patrick
A comparative synteny map of Burkholderia species links large-scale genome rearrangements to fine-scale nucleotide variation in prokaryotes Journal Article
In: Mol Biol Evol, vol. 25, no. 3, pp. 549–558, 2008, ISSN: 1537-1719.
Abstract | Links | BibTeX | Tags:
@article{pmid18162473b,
title = {A comparative synteny map of Burkholderia species links large-scale genome rearrangements to fine-scale nucleotide variation in prokaryotes},
author = {Chi Ho Lin and Guillaume Bourque and Patrick Tan},
doi = {10.1093/molbev/msm282},
issn = {1537-1719},
year = {2008},
date = {2008-03-01},
journal = {Mol Biol Evol},
volume = {25},
number = {3},
pages = {549--558},
abstract = {Genome rearrangement events, including inversions and translocations, are frequently observed across related microbial species, but the impact of such events on functional diversity is unclear. To clarify this relationship, we compared 4 members of the Gram-negative Burkholderia family (Burkholderia pseudomallei, Burkholderia mallei, Burkholderia thailandensis, and Burkholderia cenocepacia) and identified a core set of 2,590 orthologs present in all 4 species (metagenes). The metagenes were organized into 255 synteny blocks whose relative order has been altered by a predicted minimum of 242 genome rearrangement events. Functionally, metagenes within individual synteny blocks were often related. The molecular divergence of metagenes adjacent to synteny breakpoints (boundary metagenes) was significantly greater compared with metagenes within blocks, suggesting an association between breakpoint locations and local fine-scale nucleotide alterations. This phenomenon, referred to as boundary element associated divergence, was also observed in Pseudomonas and Shigella, suggesting that this is a common phenomenon in prokaryotes. We also observed preferential localization of species-specific genes and insertion sequence element to synteny breakpoints in Burkholderia. Our results suggest that in prokaryotes, genome rearrangements may influence functional diversity through the enhanced divergence of boundary genes and the creation of foci for acquiring and deleting species-specific genes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tesler, Glenn; Bourque, Guillaume
Computational tools for the analysis of rearrangements in mammalian genomes Journal Article
In: Methods Mol Biol, vol. 422, pp. 145–170, 2008, ISSN: 1064-3745.
Abstract | Links | BibTeX | Tags:
@article{pmid18629666b,
title = {Computational tools for the analysis of rearrangements in mammalian genomes},
author = {Glenn Tesler and Guillaume Bourque},
doi = {10.1007/978-1-59745-581-7_10},
issn = {1064-3745},
year = {2008},
date = {2008-01-01},
journal = {Methods Mol Biol},
volume = {422},
pages = {145--170},
abstract = {The chromosomes of mammalian genomes exhibit reasonably high levels of similarity that can be used to study small-scale sequence variations. A different approach is to study the evolutionary history of rearrangements in entire genomes based on the analysis of gene or segment orders. We describe three computational tools (GRIMM-Synteny, GRIMM, and MGR) that can be used separately or in succession to contrast different organisms at the genome-level to exploit large-scale rearrangements as a phylogenetic character.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2007
Pontius, Joan U; Mullikin, James C; Smith, Douglas R; ; Lindblad-Toh, Kerstin; Gnerre, Sante; Clamp, Michele; Chang, Jean; Stephens, Robert; Neelam, Beena; Volfovsky, Natalia; Schäffer, Alejandro A; Agarwala, Richa; Narfström, Kristina; Murphy, William J; Giger, Urs; Roca, Alfred L; Antunes, Agostinho; Menotti-Raymond, Marilyn; Yuhki, Naoya; Pecon-Slattery, Jill; Johnson, Warren E; Bourque, Guillaume; Tesler, Glenn; ; O'Brien, Stephen J
Initial sequence and comparative analysis of the cat genome Journal Article
In: Genome Res, vol. 17, no. 11, pp. 1675–1689, 2007, ISSN: 1088-9051.
Abstract | Links | BibTeX | Tags:
@article{pmid17975172b,
title = {Initial sequence and comparative analysis of the cat genome},
author = {Joan U Pontius and James C Mullikin and Douglas R Smith and and Kerstin Lindblad-Toh and Sante Gnerre and Michele Clamp and Jean Chang and Robert Stephens and Beena Neelam and Natalia Volfovsky and Alejandro A Schäffer and Richa Agarwala and Kristina Narfström and William J Murphy and Urs Giger and Alfred L Roca and Agostinho Antunes and Marilyn Menotti-Raymond and Naoya Yuhki and Jill Pecon-Slattery and Warren E Johnson and Guillaume Bourque and Glenn Tesler and and Stephen J O'Brien},
doi = {10.1101/gr.6380007},
issn = {1088-9051},
year = {2007},
date = {2007-11-01},
journal = {Genome Res},
volume = {17},
number = {11},
pages = {1675--1689},
abstract = {The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing approximately 65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Zhao, Xiao Dong; Han, Xu; Chew, Joon Lin; Liu, Jun; Chiu, Kuo Ping; Choo, Andre; Orlov, Yuriy L; Sung, Wing-Kin; Shahab, Atif; Kuznetsov, Vladimir A; Bourque, Guillaume; Oh, Steve; Ruan, Yijun; Ng, Huck-Hui; Wei, Chia-Lin
Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells Journal Article
In: Cell Stem Cell, vol. 1, no. 3, pp. 286–298, 2007, ISSN: 1875-9777.
Abstract | Links | BibTeX | Tags:
@article{pmid18371363b,
title = {Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells},
author = {Xiao Dong Zhao and Xu Han and Joon Lin Chew and Jun Liu and Kuo Ping Chiu and Andre Choo and Yuriy L Orlov and Wing-Kin Sung and Atif Shahab and Vladimir A Kuznetsov and Guillaume Bourque and Steve Oh and Yijun Ruan and Huck-Hui Ng and Chia-Lin Wei},
doi = {10.1016/j.stem.2007.08.004},
issn = {1875-9777},
year = {2007},
date = {2007-09-01},
journal = {Cell Stem Cell},
volume = {1},
number = {3},
pages = {286--298},
abstract = {Epigenetic modifications are crucial for proper lineage specification and embryo development. To explore the chromatin modification landscapes in human ES cells, we profiled two histone modifications, H3K4me3 and H3K27me3, by ChIP coupled with the paired-end ditags sequencing strategy. H3K4me3 was found to be a prevalent mark and occurred in close proximity to the promoters of two-thirds of total human genes. Among the H3K27me3 loci identified, 56% are associated with promoters and the vast majority of them are comodified by H3K4me3. By deep-transcript digital counting, 80% of H3K4me3 and 36% of comodified promoters were found to be transcribed. Remarkably, we observed that different combinations of histone methylations are associated with genes from distinct functional categories. These global histone methylation maps provide an epigenetic framework that enables the discovery of novel transcriptional networks and delineation of different genetic compartments of the pluripotent cell genome.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ruan, Yijun; Ooi, Hong Sain; Choo, Siew Woh; Chiu, Kuo Ping; Zhao, Xiao Dong; Srinivasan, K G; Yao, Fei; Choo, Chiou Yu; Liu, Jun; Ariyaratne, Pramila; Bin, Wilson G W; Kuznetsov, Vladimir A; Shahab, Atif; Sung, Wing-Kin; Bourque, Guillaume; Palanisamy, Nallasivam; Wei, Chia-Lin
Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs) Journal Article
In: Genome Res, vol. 17, no. 6, pp. 828–838, 2007, ISSN: 1088-9051.
Abstract | Links | BibTeX | Tags:
@article{pmid17568001b,
title = {Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs)},
author = {Yijun Ruan and Hong Sain Ooi and Siew Woh Choo and Kuo Ping Chiu and Xiao Dong Zhao and K G Srinivasan and Fei Yao and Chiou Yu Choo and Jun Liu and Pramila Ariyaratne and Wilson G W Bin and Vladimir A Kuznetsov and Atif Shahab and Wing-Kin Sung and Guillaume Bourque and Nallasivam Palanisamy and Chia-Lin Wei},
doi = {10.1101/gr.6018607},
issn = {1088-9051},
year = {2007},
date = {2007-06-01},
journal = {Genome Res},
volume = {17},
number = {6},
pages = {828--838},
abstract = {Identification of unconventional functional features such as fusion transcripts is a challenging task in the effort to annotate all functional DNA elements in the human genome. Paired-End diTag (PET) analysis possesses a unique capability to accurately and efficiently characterize the two ends of DNA fragments, which may have either normal or unusual compositions. This unique nature of PET analysis makes it an ideal tool for uncovering unconventional features residing in the human genome. Using the PET approach for comprehensive transcriptome analysis, we were able to identify fusion transcripts derived from genome rearrangements and actively expressed retrotransposed pseudogenes, which would be difficult to capture by other means. Here, we demonstrate this unique capability through the analysis of 865,000 individual transcripts in two types of cancer cells. In addition to the characterization of a large number of differentially expressed alternative 5' and 3' transcript variants and novel transcriptional units, we identified 70 fusion transcript candidates in this study. One was validated as the product of a fusion gene between BCAS4 and BCAS3 resulting from an amplification followed by a translocation event between the two loci, chr20q13 and chr17q23. Through an examination of PETs that mapped to multiple genomic locations, we identified 4055 retrotransposed loci in the human genome, of which at least three were found to be transcriptionally active. The PET mapping strategy presented here promises to be a useful tool in annotating the human genome, especially aberrations in human cancer genomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lin, Chin-Yo; Vega, Vinsensius B; Thomsen, Jane S; Zhang, Tao; Kong, Say Li; Xie, Min; Chiu, Kuo Ping; Lipovich, Leonard; Barnett, Daniel H; Stossi, Fabio; Yeo, Ailing; George, Joshy; Kuznetsov, Vladimir A; Lee, Yew Kok; Charn, Tze Howe; Palanisamy, Nallasivam; Miller, Lance D; Cheung, Edwin; Katzenellenbogen, Benita S; Ruan, Yijun; Bourque, Guillaume; Wei, Chia-Lin; Liu, Edison T
Whole-genome cartography of estrogen receptor alpha binding sites Journal Article
In: PLoS Genet, vol. 3, no. 6, pp. e87, 2007, ISSN: 1553-7404.
Abstract | Links | BibTeX | Tags:
@article{pmid17542648b,
title = {Whole-genome cartography of estrogen receptor alpha binding sites},
author = {Chin-Yo Lin and Vinsensius B Vega and Jane S Thomsen and Tao Zhang and Say Li Kong and Min Xie and Kuo Ping Chiu and Leonard Lipovich and Daniel H Barnett and Fabio Stossi and Ailing Yeo and Joshy George and Vladimir A Kuznetsov and Yew Kok Lee and Tze Howe Charn and Nallasivam Palanisamy and Lance D Miller and Edwin Cheung and Benita S Katzenellenbogen and Yijun Ruan and Guillaume Bourque and Chia-Lin Wei and Edison T Liu},
doi = {10.1371/journal.pgen.0030087},
issn = {1553-7404},
year = {2007},
date = {2007-06-01},
journal = {PLoS Genet},
volume = {3},
number = {6},
pages = {e87},
abstract = {Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERalpha binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERalpha-positive from ERalpha-negative breast tumors. The expression dynamics of the genes adjacent to ERalpha binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERalpha appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona fide human ERalpha binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERalpha binding and gene regulation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2006
Xu, Jun; Srinivas, Bhylahalli P; Tay, Shang Yew; Mak, Alicia; Yu, Xianwen; Lee, Serene G P; Yang, Henry; Govindarajan, Kunde R; Leong, Bernard; Bourque, Guillaume; Mathavan, Sinnakarupan; Roy, Sudipto
Genomewide expression profiling in the zebrafish embryo identifies target genes regulated by Hedgehog signaling during vertebrate development Journal Article
In: Genetics, vol. 174, no. 2, pp. 735–752, 2006, ISSN: 0016-6731.
Abstract | Links | BibTeX | Tags:
@article{pmid16888327b,
title = {Genomewide expression profiling in the zebrafish embryo identifies target genes regulated by Hedgehog signaling during vertebrate development},
author = {Jun Xu and Bhylahalli P Srinivas and Shang Yew Tay and Alicia Mak and Xianwen Yu and Serene G P Lee and Henry Yang and Kunde R Govindarajan and Bernard Leong and Guillaume Bourque and Sinnakarupan Mathavan and Sudipto Roy},
doi = {10.1534/genetics.106.061523},
issn = {0016-6731},
year = {2006},
date = {2006-10-01},
journal = {Genetics},
volume = {174},
number = {2},
pages = {735--752},
abstract = {Hedgehog proteins play critical roles in organizing the embryonic development of animals, largely through modulation of target gene expression. Little is currently known, however, about the kinds and numbers of genes whose expression is controlled, directly or indirectly, by Hedgehog activity. Using techniques to globally repress or activate Hedgehog signaling in zebrafish embryos followed by microarray-based expression profiling, we have discovered a cohort of genes whose expression responds significantly to loss or gain of Hedgehog function. We have confirmed the Hedgehog responsiveness of a representative set of these genes with whole-mount in situ hybridization as well as real time PCR. In addition, we show that the consensus Gli-binding motif is enriched within the putative regulatory elements of a sizeable proportion of genes that showed positive regulation in our assay, indicating that their expression is directly induced by Hedgehog. Finally, we provide evidence that the Hedgehog-dependent spatially restricted transcription of one such gene, nkx2.9, is indeed mediated by Gli1 through a single Gli recognition site located within an evolutionarily conserved enhancer fragment. Taken together, this study represents the first comprehensive survey of target genes regulated by the Hedgehog pathway during vertebrate development. Our data also demonstrate for the first time the functionality of the Gli-binding motif in the control of Hedgehog signaling-induced gene expression in the zebrafish embryo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Loh, Yuin-Han; Wu, Qiang; Chew, Joon-Lin; Vega, Vinsensius B; Zhang, Weiwei; Chen, Xi; Bourque, Guillaume; George, Joshy; Leong, Bernard; Liu, Jun; Wong, Kee-Yew; Sung, Ken W; Lee, Charlie W H; Zhao, Xiao-Dong; Chiu, Kuo-Ping; Lipovich, Leonard; Kuznetsov, Vladimir A; Robson, Paul; Stanton, Lawrence W; Wei, Chia-Lin; Ruan, Yijun; Lim, Bing; Ng, Huck-Hui
The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells Journal Article
In: Nat Genet, vol. 38, no. 4, pp. 431–440, 2006, ISSN: 1061-4036.
Abstract | Links | BibTeX | Tags:
@article{pmid16518401b,
title = {The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells},
author = {Yuin-Han Loh and Qiang Wu and Joon-Lin Chew and Vinsensius B Vega and Weiwei Zhang and Xi Chen and Guillaume Bourque and Joshy George and Bernard Leong and Jun Liu and Kee-Yew Wong and Ken W Sung and Charlie W H Lee and Xiao-Dong Zhao and Kuo-Ping Chiu and Leonard Lipovich and Vladimir A Kuznetsov and Paul Robson and Lawrence W Stanton and Chia-Lin Wei and Yijun Ruan and Bing Lim and Huck-Hui Ng},
doi = {10.1038/ng1760},
issn = {1061-4036},
year = {2006},
date = {2006-04-01},
journal = {Nat Genet},
volume = {38},
number = {4},
pages = {431--440},
abstract = {Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse ES cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis-acting elements mediating their respective binding to genomic sites. By integrating RNA interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep ES cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bourque, Guillaume; Tesler, Glenn; Pevzner, Pavel A
The convergence of cytogenetics and rearrangement-based models for ancestral genome reconstruction Journal Article
In: Genome Res, vol. 16, no. 3, pp. 311–313, 2006, ISSN: 1088-9051.
@article{pmid16510896b,
title = {The convergence of cytogenetics and rearrangement-based models for ancestral genome reconstruction},
author = {Guillaume Bourque and Glenn Tesler and Pavel A Pevzner},
doi = {10.1101/gr.4631806},
issn = {1088-9051},
year = {2006},
date = {2006-03-01},
journal = {Genome Res},
volume = {16},
number = {3},
pages = {311--313},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Vega, Vinsensius B; Lin, Chin-Yo; Lai, Koon Siew; Kong, Say Li; Xie, Min; Su, Xiaodi; Teh, Huey Fang; Thomsen, Jane S; Yeo, Ai Li; Sung, Wing Kin; Bourque, Guillaume; Liu, Edison T
Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites Journal Article
In: Genome Biol, vol. 7, no. 9, pp. R82, 2006, ISSN: 1474-760X.
Abstract | Links | BibTeX | Tags:
@article{pmid16961928b,
title = {Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites},
author = {Vinsensius B Vega and Chin-Yo Lin and Koon Siew Lai and Say Li Kong and Min Xie and Xiaodi Su and Huey Fang Teh and Jane S Thomsen and Ai Li Yeo and Wing Kin Sung and Guillaume Bourque and Edison T Liu},
doi = {10.1186/gb-2006-7-9-r82},
issn = {1474-760X},
year = {2006},
date = {2006-01-01},
journal = {Genome Biol},
volume = {7},
number = {9},
pages = {R82},
abstract = {BACKGROUND: Transcription factor binding sites (TFBS) impart specificity to cellular transcriptional responses and have largely been defined by consensus motifs derived from a handful of validated sites. The low specificity of the computational predictions of TFBSs has been attributed to ubiquity of the motifs and the relaxed sequence requirements for binding. We posited that the inadequacy is due to limited input of empirically verified sites, and demonstrated a multiplatform approach to constructing a robust model.
RESULTS: Using the TFBS for the estrogen receptor (ER)alpha (estrogen response element [ERE]) as a model system, we extracted EREs from multiple molecular and genomic platforms whose binding to ERalpha has been experimentally confirmed or rejected. In silico analyses revealed significant sequence information flanking the standard binding consensus, discriminating ERE-like sequences that bind ERalpha from those that are nonbinders. We extended the ERE consensus by three bases, bearing a terminal G at the third position 3' and an initiator C at the third position 5', which were further validated using surface plasmon resonance spectroscopy. Our functional human ERE prediction algorithm (h-ERE) outperformed existing predictive algorithms and produced fewer than 5% false negatives upon experimental validation.
CONCLUSION: Building upon a larger experimentally validated ERE set, the h-ERE algorithm is able to demarcate better the universe of ERE-like sequences that are potential ER binders. Only 14% of the predicted optimal binding sites were utilized under the experimental conditions employed, pointing to other selective criteria not related to EREs. Other factors, in addition to primary nucleotide sequence, will ultimately determine binding site selection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RESULTS: Using the TFBS for the estrogen receptor (ER)alpha (estrogen response element [ERE]) as a model system, we extracted EREs from multiple molecular and genomic platforms whose binding to ERalpha has been experimentally confirmed or rejected. In silico analyses revealed significant sequence information flanking the standard binding consensus, discriminating ERE-like sequences that bind ERalpha from those that are nonbinders. We extended the ERE consensus by three bases, bearing a terminal G at the third position 3' and an initiator C at the third position 5', which were further validated using surface plasmon resonance spectroscopy. Our functional human ERE prediction algorithm (h-ERE) outperformed existing predictive algorithms and produced fewer than 5% false negatives upon experimental validation.
CONCLUSION: Building upon a larger experimentally validated ERE set, the h-ERE algorithm is able to demarcate better the universe of ERE-like sequences that are potential ER binders. Only 14% of the predicted optimal binding sites were utilized under the experimental conditions employed, pointing to other selective criteria not related to EREs. Other factors, in addition to primary nucleotide sequence, will ultimately determine binding site selection.
2005
Yu, Hong Xiang; Chia, Jer-Ming; Bourque, Guillaume; Wong, Marie Vivien; Chan, Soh Ha; Ren, Ee Chee
A population-based LD map of the human chromosome 6p Journal Article
In: Immunogenetics, vol. 57, no. 8, pp. 559–565, 2005, ISSN: 0093-7711.
Abstract | Links | BibTeX | Tags:
@article{pmid16133449b,
title = {A population-based LD map of the human chromosome 6p},
author = {Hong Xiang Yu and Jer-Ming Chia and Guillaume Bourque and Marie Vivien Wong and Soh Ha Chan and Ee Chee Ren},
doi = {10.1007/s00251-005-0002-4},
issn = {0093-7711},
year = {2005},
date = {2005-09-01},
journal = {Immunogenetics},
volume = {57},
number = {8},
pages = {559--565},
abstract = {The recent publication of the complete sequence of human chromosome 6 provides a platform from which to investigate genomic sequence variation. We report here a detailed linkage disequilibrium (LD) pattern map across the entire human chromosome 6p by using a set of 1152 single nucleotide polymorphisms (SNPs) in a population of 198 Singaporean Chinese, with 326 SNPs focused in the major histocompatibility complex (MHC) region. Our analysis shows some unexpectedly high segments of strong LD in a 10-Mb region that includes the extremely polymorphic and gene-rich MHC loci and many non-MHC genes. These include the telomeric peri-MHC region that harbors olfactory receptors, histones and zinc finger clusters, and the centromeric peri-MHC region that contains several unknown open reading frames. The data also help refine a human-mouse synteny break in the region between 28.6 and 29.4 Mb. The population-based LD map presented here will provide an essential resource for understanding the genomic sequence variation of chromosome 6p and LD mapping of disease genes of complex genetic traits.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Murphy, William J; Larkin, Denis M; der Wind, Annelie Everts-van; Bourque, Guillaume; Tesler, Glenn; Auvil, Loretta; Beever, Jonathan E; Chowdhary, Bhanu P; Galibert, Francis; Gatzke, Lisa; Hitte, Christophe; Meyers, Stacey N; Milan, Denis; Ostrander, Elaine A; Pape, Greg; Parker, Heidi G; Raudsepp, Terje; Rogatcheva, Margarita B; Schook, Lawrence B; Skow, Loren C; Welge, Michael; Womack, James E; O'brien, Stephen J; Pevzner, Pavel A; Lewin, Harris A
Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps Journal Article
In: Science, vol. 309, no. 5734, pp. 613–617, 2005, ISSN: 1095-9203.
Abstract | Links | BibTeX | Tags:
@article{pmid16040707b,
title = {Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps},
author = {William J Murphy and Denis M Larkin and Annelie Everts-van der Wind and Guillaume Bourque and Glenn Tesler and Loretta Auvil and Jonathan E Beever and Bhanu P Chowdhary and Francis Galibert and Lisa Gatzke and Christophe Hitte and Stacey N Meyers and Denis Milan and Elaine A Ostrander and Greg Pape and Heidi G Parker and Terje Raudsepp and Margarita B Rogatcheva and Lawrence B Schook and Loren C Skow and Michael Welge and James E Womack and Stephen J O'brien and Pavel A Pevzner and Harris A Lewin},
doi = {10.1126/science.1111387},
issn = {1095-9203},
year = {2005},
date = {2005-07-01},
journal = {Science},
volume = {309},
number = {5734},
pages = {613--617},
abstract = {The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bourque, Guillaume; Zdobnov, Evgeny M; Bork, Peer; Pevzner, Pavel A; Tesler, Glenn
Comparative architectures of mammalian and chicken genomes reveal highly variable rates of genomic rearrangements across different lineages Journal Article
In: Genome Res, vol. 15, no. 1, pp. 98–110, 2005, ISSN: 1088-9051.
Abstract | Links | BibTeX | Tags:
@article{pmid15590940b,
title = {Comparative architectures of mammalian and chicken genomes reveal highly variable rates of genomic rearrangements across different lineages},
author = {Guillaume Bourque and Evgeny M Zdobnov and Peer Bork and Pavel A Pevzner and Glenn Tesler},
doi = {10.1101/gr.3002305},
issn = {1088-9051},
year = {2005},
date = {2005-01-01},
journal = {Genome Res},
volume = {15},
number = {1},
pages = {98--110},
abstract = {Molecular evolution studies are usually based on the analysis of individual genes and thus reflect only small-range variations in genomic sequences. A complementary approach is to study the evolutionary history of rearrangements in entire genomes based on the analysis of gene orders. The progress in whole genome sequencing provides an unprecedented level of detailed sequence data to infer genome rearrangements through comparative approaches. The comparative analysis of recently sequenced rodent genomes with the human genome revealed evidence for a larger number of rearrangements than previously thought and led to the reconstruction of the putative genomic architecture of the murid rodent ancestor, while the architecture of the ancestral mammalian genome and the rate of rearrangements in the human lineage remained unknown. Sequencing the chicken genome provides an opportunity to reconstruct the architecture of the ancestral mammalian genome by using chicken as an outgroup. Our analysis reveals a very low rate of rearrangements and, in particular, interchromosomal rearrangements in chicken, in the early mammalian ancestor, or in both. The suggested number of interchromosomal rearrangements between the mammalian ancestor and chicken, during an estimated 500 million years of evolution, only slightly exceeds the number of interchromosomal rearrangements that happened in the mouse lineage, over the course of about 87 million years.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2004
Bourque, Guillaume; Sankoff, David
Improving gene network inference by comparing expression time-series across species, developmental stages or tissues Journal Article
In: J Bioinform Comput Biol, vol. 2, no. 4, pp. 765–783, 2004, ISSN: 0219-7200.
Abstract | Links | BibTeX | Tags:
@article{pmid15617165b,
title = {Improving gene network inference by comparing expression time-series across species, developmental stages or tissues},
author = {Guillaume Bourque and David Sankoff},
doi = {10.1142/s0219720004000892},
issn = {0219-7200},
year = {2004},
date = {2004-12-01},
journal = {J Bioinform Comput Biol},
volume = {2},
number = {4},
pages = {765--783},
abstract = {We present a method for gene network inference and revision based on time-series data. Gene networks are modeled using linear differential equations and a generalized stepwise multiple linear regression procedure is used to recover the interaction coefficients. Our system is designed for the recovery of gene interactions concurrently in many gene regulatory networks related by a tree or a more general graph. We show how this comparative framework can facilitate the recovery of the networks and improve the quality of the solutions inferred.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bourque, Guillaume; Pevzner, Pavel A; Tesler, Glenn
Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes Journal Article
In: Genome Res, vol. 14, no. 4, pp. 507–516, 2004, ISSN: 1088-9051.
Abstract | Links | BibTeX | Tags:
@article{pmid15059991b,
title = {Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes},
author = {Guillaume Bourque and Pavel A Pevzner and Glenn Tesler},
doi = {10.1101/gr.1975204},
issn = {1088-9051},
year = {2004},
date = {2004-04-01},
journal = {Genome Res},
volume = {14},
number = {4},
pages = {507--516},
abstract = {Recent analysis of genome rearrangements in human and mouse genomes revealed evidence for more rearrangements than thought previously and shed light on previously unknown features of mammalian evolution, like breakpoint reuse and numerous microrearrangements. However, two-way analysis cannot reveal the genomic architecture of ancestral mammals or assign rearrangement events to different lineages. Thus, the "original synteny" problem introduced by Nadeau and Sankoff previously, remains unsolved, as at least three mammalian genomes are required to derive the ancestral mammalian karyotype. We show that availability of the rat genome allows one to reconstruct a putative genomic architecture of the ancestral murid rodent genome. This reconstruction suggests that this ancestral genome retained many previously postulated chromosome associations in the placental ancestor and reveals others that were beyond the resolution of cytogenetic, radiation hybrid mapping, and chromosome painting techniques. Three-way analysis of rearrangements leads to a reliable reconstruction of the genomic architecture of specific regions in the murid ancestor, including the X chromosome, and for the first time allows one to assign major rearrangement events to one of human, mouse, and rat lineages. Our analysis implies that the rate of rearrangements is much higher in murid rodents than in the human lineage and confirms the existence of rearrangement hot-spots in all three lineages.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2003
Murphy, William J; Bourque, Guillaume; Tesler, Glenn; Pevzner, Pavel; O'Brien, Stephen J
Reconstructing the genomic architecture of mammalian ancestors using multispecies comparative maps Journal Article
In: Hum Genomics, vol. 1, no. 1, pp. 30–40, 2003, ISSN: 1473-9542.
Abstract | Links | BibTeX | Tags:
@article{pmid15601531b,
title = {Reconstructing the genomic architecture of mammalian ancestors using multispecies comparative maps},
author = {William J Murphy and Guillaume Bourque and Glenn Tesler and Pavel Pevzner and Stephen J O'Brien},
doi = {10.1186/1479-7364-1-1-30},
issn = {1473-9542},
year = {2003},
date = {2003-11-01},
journal = {Hum Genomics},
volume = {1},
number = {1},
pages = {30--40},
abstract = {Rapidly developing comparative gene maps in selected mammal species are providing an opportunity to reconstruct the genomic architecture of mammalian ancestors and study rearrangements that transformed this ancestral genome into existing mammalian genomes. Here, the recently developed Multiple Genome Rearrangement (MGR) algorithm is applied to human, mouse, cat and cattle comparative maps (with 311-470 shared markers) to impute the ancestral mammalian genome. Reconstructed ancestors consist of 70-100 conserved segments shared across the genomes that have been exchanged by rearrangement events along the ordinal lineages leading to modern species genomes. Genomic distances between species, dominated by inversions (reversals) and translocations, are presented in a first multispecies attempt using ordered mapping data to reconstruct the evolutionary exchanges that preceded modern placental mammal genomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2002
Bourque, Guillaume; Pevzner, Pavel A
Genome-scale evolution: reconstructing gene orders in the ancestral species
2002.
@{pmid11779828b,
title = {Genome-scale evolution: reconstructing gene orders in the ancestral species},
author = {Guillaume Bourque and Pavel A Pevzner},
issn = {1088-9051},
year = {2002},
date = {2002-01-01},
journal = {Genome Res},
volume = {12},
number = {1},
pages = {26--36},
abstract = {Recent progress in genome-scale sequencing and comparative mapping raises new challenges in studies of genome rearrangements. Although the pairwise genome rearrangement problem is well-studied, algorithms for reconstructing rearrangement scenarios for multiple species are in great need. The previous approaches to multiple genome rearrangement problem were largely based on the breakpoint distance rather than on a more biologically accurate rearrangement (reversal) distance. Another shortcoming of the existing software tools is their inability to analyze rearrangements (inversions, translocations, fusions, and fissions) of multichromosomal genomes. This paper proposes a new multiple genome rearrangement algorithm that is based on the rearrangement (rather than breakpoint) distance and that is applicable to both unichromosomal and multichromosomal genomes. We further apply this algorithm for genome-scale phylogenetic tree reconstruction and deriving ancestral gene orders. In particular, our analysis suggests a new improved rearrangement scenario for a very difficult Campanulaceae cpDNA dataset and a putative rearrangement scenario for human, mouse and cat genomes.},
keywords = {},
pubstate = {published},
tppubtype = {}
}
0000
Donovan, Chan; Xiaojian, Shao; Marie-Charlotte, Dumargne; Mahmoud, Aarabi; Marie-Michelle, Simon; Tony, Kwan; L., Bailey Janice; Bernard, Robaire; Sarah, Kimmins; C., San Gabriel Maria; Armand, Zini; Clifford, Librach; Sergey, Moskovtsev; Elin, Grundberg; Guillaume, Bourque; Tomi, Pastinen; M., Trasler Jacquetta
Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism Journal Article
In: Environmental Health Perspectives, vol. 127, no. 8, pp. 087002, 0000, (Publisher: Environmental Health Perspectives).
Abstract | Links | BibTeX | Tags:
@article{chan_donovan_customized_nodate,
title = {Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism},
author = {Chan Donovan and Shao Xiaojian and Dumargne Marie-Charlotte and Aarabi Mahmoud and Simon Marie-Michelle and Kwan Tony and Bailey Janice L. and Robaire Bernard and Kimmins Sarah and San Gabriel Maria C. and Zini Armand and Librach Clifford and Moskovtsev Sergey and Grundberg Elin and Bourque Guillaume and Pastinen Tomi and Trasler Jacquetta M.},
url = {https://ehp.niehs.nih.gov/doi/10.1289/EHP4812},
doi = {10.1289/EHP4812},
urldate = {2021-05-26},
journal = {Environmental Health Perspectives},
volume = {127},
number = {8},
pages = {087002},
abstract = {Background:The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements.Objectives:Our goal was to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome.Methods:To characterize variation in sperm DNA methylation, we performed whole genome bisulfite sequencing (WGBS) on an equimolar pool of sperm DNA from a wide cross section of 30 men varying in age, fertility status, methylenetetrahydrofolate reductase (MTHFR) genotype, and exposures. With our targeted capture panel, in individual samples, we examined the effect of MTHFR genotype (n=13n=13textlessmath alttext="n equals 13" display="inline" overflow="scroll"textgreatertextlessmrowtextgreatertextlessmitextgreaterntextless/mitextgreatertextlessmotextgreater=textless/motextgreatertextlessmntextgreater13textless/mntextgreatertextless/mrowtextgreatertextless/mathtextgreater677CC},
note = {Publisher: Environmental Health Perspectives},
keywords = {},
pubstate = {published},
tppubtype = {article}
}