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| Content Provider | PubMed Central |
|---|---|
| Author | Mason, Christopher E. Shu, Feng-jue Wang, Cheng Session, Ryan M. Kallen, Roland G. Sidell, Neil Yu, Tianwei Liu, Mei Hui Cheung, Edwin Kallen, Caleb B. |
| Copyright Year | 2010 |
| Abstract | Location analysis for estrogen receptor-α (ERα)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERα-bound loci and quantify the incidence of ERE sequences under two stringencies of detection: <10% and 10–20% nucleotide deviation from the canonical ERE sequence. We demonstrate that ∼50% of all ERα-bound loci do not have a discernable ERE and show that most ERα-bound EREs are not perfect consensus EREs. Approximately one-third of all ERα-bound ERE sequences reside within repetitive DNA sequences, most commonly of the AluS family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets. Diverse ERα-bound loci were validated using electrophoretic mobility shift assay and ChIP-polymerase chain reaction (PCR). The functional significance of receptor-bound loci was demonstrated using luciferase reporter assays which proved that repetitive element ERE sequences contribute to enhancer function. ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to these loci in vivo. Our data demonstrate that ERα binds to widely variant EREs with less sequence specificity than had previously been suspected and that binding at repetitive and nonrepetitive genomic targets is favored by specific trinucleotide spacers. |
| Related Links | http://dx.doi.org/10.1093/nar/gkp1188 |
| Ending Page | 2368 |
| Page Count | 14 |
| Starting Page | 2355 |
| File Format | |
| ISSN | 03051048 |
| e-ISSN | 13624962 |
| Journal | Nucleic Acids Research |
| Issue Number | 7 |
| Volume Number | 38 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2010-04-01 |
| Access Restriction | Open |
| Rights Holder | Oxford University Press |
| Subject Keyword | Genetics Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
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