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

19 Citations (Scopus)

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 - 2014
Externally publishedYes

Fingerprint

Polycomb Repressive Complex 2
Chromatin
Multigene Family
Tretinoin
Histones
Lysine
Cluster Analysis
Vertebrates
CCCTC-binding factor
Chromosomes
Binding Sites

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells. / Xu, Miao; Zhao, Guang Nian; Lv, Xiang; Liu, Guoyou; Wang, Lily Yan; Hao, De Long; Wang, Junwen; Liu, De Pei; Liang, Chih Chuan.

In: Molecular and Cellular Biology, Vol. 34, No. 20, 2014, p. 3867-3879.

Research output: Contribution to journalArticle

Xu, Miao ; Zhao, Guang Nian ; Lv, Xiang ; Liu, Guoyou ; Wang, Lily Yan ; Hao, De Long ; Wang, Junwen ; Liu, De Pei ; Liang, Chih Chuan. / CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells. In: Molecular and Cellular Biology. 2014 ; Vol. 34, No. 20. pp. 3867-3879.
@article{c5bc4db300724e4995f5ab5cf89cb1e9,
title = "CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells",
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.",
author = "Miao Xu and Zhao, {Guang Nian} and Xiang Lv and Guoyou Liu and Wang, {Lily Yan} and Hao, {De Long} and Junwen Wang and Liu, {De Pei} and Liang, {Chih Chuan}",
year = "2014",
doi = "10.1128/MCB.00567-14",
language = "English (US)",
volume = "34",
pages = "3867--3879",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "20",

}

TY - JOUR

T1 - CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells

AU - Xu, Miao

AU - Zhao, Guang Nian

AU - Lv, Xiang

AU - Liu, Guoyou

AU - Wang, Lily Yan

AU - Hao, De Long

AU - Wang, Junwen

AU - Liu, De Pei

AU - Liang, Chih Chuan

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907152997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907152997&partnerID=8YFLogxK

U2 - 10.1128/MCB.00567-14

DO - 10.1128/MCB.00567-14

M3 - Article

C2 - 25135475

AN - SCOPUS:84907152997

VL - 34

SP - 3867

EP - 3879

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 20

ER -