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A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection

Identifieur interne : 002408 ( Main/Exploration ); précédent : 002407; suivant : 002409

A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection

Auteurs : Zhong Deng [États-Unis] ; Zhuo Wang [États-Unis] ; Nick Stong [États-Unis] ; Robert Plasschaert [États-Unis] ; Aliah Moczan [États-Unis] ; Horng-Shen Chen [États-Unis] ; Sufeng Hu [États-Unis] ; Priyankara Wikramasinghe [États-Unis] ; Ramana V. Davuluri [États-Unis] ; Marisa S. Bartolomei [États-Unis] ; Harold Riethman [États-Unis] ; Paul M. Lieberman [États-Unis]

Source :

RBID : ISTEX:F79218B8EAA6F727BA0CCF7A35D28AB6C07FB87A

English descriptors

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.
ChIP‐seq analyses reveal a common subtelomeric CTCF‐ and cohesion‐binding site important for RNA polymerase recruitment and TERRA transcription.

Url:
DOI: 10.1038/emboj.2012.266


Affiliations:


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<term>Binding factors</term>
<term>Binding sites</term>
<term>Biol</term>
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<term>Luciferase activity</term>
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<term>Primer sets</term>
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<term>Sicontrol</term>
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<term>Subtelomeres</term>
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<term>Subunit</term>
<term>Supplementary figure</term>
<term>Supplementary figures</term>
<term>Supplementary table</term>
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<term>Transcription regulation</term>
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<term>U2os cells</term>
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<div type="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.</div>
<div type="abstract">ChIP‐seq analyses reveal a common subtelomeric CTCF‐ and cohesion‐binding site important for RNA polymerase recruitment and TERRA transcription.</div>
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