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Whole-Genome Cartography of Estrogen Receptor α Binding Sites
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lin, Chin Y. Vega, Vinsensius B. Thomsen, Jane Sohn 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. |
| Copyright Year | 2007 |
| 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. |
| Starting Page | 5977 |
| Ending Page | 5983 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/84/e8/pgen.0030087.PMC1885282.pdf |
| PubMed reference number | 17542648v1 |
| Volume Number | 3 |
| Journal | PLoS genetics |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Binding Sites Biopolymer Sequencing Estradiol Estrogen Receptor alpha Estrogen Receptors Estrogens Gene Expression Hepatocyte Nuclear Factor 3-alpha Introns Mammary Neoplasms Patients Projections and Predictions Repression, Psychology Response Elements Rule (guideline) TRANSCRIPTION FACTOR Transcript Transcription, Genetic Transcriptional Repression chromatin immunoprecipitation mapped promoter type I interferon receptor |
| Content Type | Text |
| Resource Type | Article |
