Title |
A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection
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Published in |
EMBO Journal, September 2012
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DOI | 10.1038/emboj.2012.266 |
Pubmed ID | |
Authors |
Zhong Deng, Zhuo Wang, Nick Stong, Robert Plasschaert, Aliah Moczan, Horng‐Shen Chen, Sufeng Hu, Priyankara Wikramasinghe, Ramana V Davuluri, Marisa S Bartolomei, Harold Riethman, Paul M Lieberman |
Abstract |
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 ∼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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 1% |
France | 2 | <1% |
Japan | 2 | <1% |
United Kingdom | 1 | <1% |
India | 1 | <1% |
Belgium | 1 | <1% |
Unknown | 192 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 58 | 29% |
Researcher | 47 | 23% |
Student > Master | 30 | 15% |
Student > Bachelor | 9 | 4% |
Professor | 8 | 4% |
Other | 22 | 11% |
Unknown | 28 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 83 | 41% |
Biochemistry, Genetics and Molecular Biology | 77 | 38% |
Medicine and Dentistry | 3 | 1% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | <1% |
Immunology and Microbiology | 1 | <1% |
Other | 1 | <1% |
Unknown | 36 | 18% |