Format

Send to

Choose Destination
Mol Cell Biol. 2014 Oct;34(20):3867-79. doi: 10.1128/MCB.00567-14. Epub 2014 Aug 18.

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

Author information

1
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
2
Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, People's Republic of China.
3
Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China Center for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, People's Republic of China.
4
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China iudp@pumc.edu.cn.

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.

PMID:
25135475
PMCID:
PMC4187707
DOI:
10.1128/MCB.00567-14
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center