CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells

Miao Xu, Guang Nian Zhao, Xiang Lv, Guoyou Liu, Lily Yan Wang, De Long Hao, Junwen Wang, De Pei Liu, Chih Chuan Liang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

HOX cluster genes are activated sequentially in their positional order along the chromosome during vertebrate development. This phenomenon, known as temporal colinearity, depends on transcriptional silencing of 5= HOX genes. Chromatin looping was recently identified as a conserved feature of silent HOX clusters, with CCCTC-binding factor (CTCF) binding sites located at the loop bases. However, the potential contribution of CTCF to HOX cluster silencing and the underlying mechanism have not been established. Here, we demonstrate that the HOXA locus is organized by CTCF into chromatin loops and that CTCF depletion causes significantly enhanced activation of HOXA3 to -A7, -A9 to -A11, and -A13 in response to retinoic acid, with the highest effect observed for HOXA9. Our subsequent analyses revealed that CTCF facilitates the stabilization of Polycomb repressive complex 2 (PRC2) and trimethylated lysine 27 of histone H3 (H3K27me3) at the human HOXA locus. Our results reveal that CTCF functions as a controller of HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure.

Original languageEnglish (US)
Pages (from-to)3867-3879
Number of pages13
JournalMolecular and cellular biology
Volume34
Issue number20
DOIs
StatePublished - Jan 1 2014

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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