NDLI: Hypermethylated in Cancer 1 (HIC1) Recruits Polycomb Repressive Complex 2 (PRC2) to a Subset of Its Target Genes through Interaction with Human Polycomb-like (hPCL) Proteins

Content Provider	Journal of Biological Chemistry (JBC)
Author	Boulay, Gaylor Dubuissez, Marion Rechem, Capucine Van Forget, Antoine Helin, Kristian Ayrault, Olivier Leprince, Dominique
Abstract	HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene epigenetically silenced or deleted in many human cancers. HIC1 is involved in regulatory loops modulating p53- and E2F1-dependent cell survival, growth control, and stress responses. HIC1 is also essential for normal development because Hic1-deficient mice die perinatally and exhibit gross developmental defects throughout the second half of development. HIC1 encodes a transcriptional repressor with five C2H2 zinc fingers mediating sequence-specific DNA binding and two repression domains: an N-terminal BTB/POZ domain and a central region recruiting CtBP and NuRD complexes. By yeast two-hybrid screening, we identified the Polycomb-like protein hPCL3 as a novel co-repressor for HIC1. Using multiple biochemical strategies, we demonstrated that HIC1 interacts with hPCL3 and its paralog PHF1 to form a stable complex with the PRC2 members EZH2, EED, and Suz12. Confirming the implication of HIC1 in Polycomb recruitment, we showed that HIC1 shares some of its target genes with PRC2, including ATOH1. Depletion of HIC1 by siRNA interference leads to a partial displacement of EZH2 from the ATOH1 promoter. Furthermore, in vivo, ATOH1 repression by HIC1 is associated with Polycomb activity during mouse cerebellar development. Thus, our results identify HIC1 as the first transcription factor in mammals able to recruit PRC2 to some target promoters through its interaction with Polycomb-like proteins.
Related Links	http://www.jbc.org/content/287/13/10509.abstract
Ending Page	10524
Starting Page	10509
Page Count	16
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	13
Volume Number	287
DOI	10.1074/jbc.M111.320234
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-03-23
Access Restriction	Open
Subject Keyword	Chromatin Epigenetics Polycomb Transcription Repressor Tumor Suppressor Gene ATOH1 HIC1 PRC2 Polycomb-like Polycomb-like hPCL3 DNA and Chromosomes
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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