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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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 ∼1-2kb 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.

Original languageEnglish (US)
Pages (from-to)4165-4178
Number of pages14
JournalEMBO Journal
Volume31
Issue number21
DOIs
StatePublished - Oct 31 2012

Keywords

  • RNA polymerase
  • histone
  • shelterin
  • subtelomere
  • telomere

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection'. Together they form a unique fingerprint.

Cite this