期刊
EMBO JOURNAL
卷 31, 期 21, 页码 4165-4178出版社
WILEY
DOI: 10.1038/emboj.2012.266
关键词
histone; RNA polymerase; shelterin; subtelomere; telomere
资金
- American Heart Association
- Philadelphia Health Care Trust
- NRSA [F31HG006395, T32GM008216]
- NIH [RO1CA140652, R21CA143349, R01HD042026]
- Wistar Cancer Center core Grant [P30 CA10815]
- Commonwealth Universal Research Enhancement Program, PA Department of Health
The contribution of human subtelomeric DNA and chromatin organization to telomere integrity and chromosome end protection is not yet understood in molecular detail. Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF-and cohesin-binding site within similar to 1-2 kb of the TTAGGG repeat tract and adjacent to a CpG-islands implicated in TERRA transcription control. ChIP-Seq also revealed that RNA polymerase II (RNAPII) was enriched at sites adjacent to the CTCF sites and extending towards the telomere repeat tracts. Mutation of CTCF-binding sites in plasmid-borne promoters reduced transcriptional activity in an orientation-dependent manner. Depletion of CTCF by shRNA led to a decrease in TERRA transcription, and a loss of cohesin and RNAPII binding to the subtelomeres. Depletion of either CTCF or cohesin subunit Rad21 caused telomere-induced DNA damage foci (TIF) formation, and destabilized TRF1 and TRF2 binding to the TTAGGG proximal subtelomere DNA. These findings indicate that CTCF and cohesin are integral components of most human subtelomeres, and important for the regulation of TERRA transcription and telomere end protection. The EMBO Journal (2012) 31, 4165-4178. doi: 10.1038/emboj.2012.266; Published online 25 September 2012
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