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PMID: 22083958 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-β-catenin signaling pathway.

Molecular and cellular biology ·Vol. 32 ·No. 2 ·2012-01-00 ·Pages 501-12

Nishiyama M, Skoultchi AI, Nakayama KI

Abstract

Members of the chromodomain helicase DNA-binding (CHD) family of proteins are thought to regulate gene expression. Among mammalian CHD proteins, CHD8 was originally isolated as a negative regulator of the Wnt-β-catenin signaling pathway that binds directly to β-catenin and suppresses its transactivation activity. The mechanism by which CHD8 inhibits β-catenin-dependent transcription has been unclear, however. Here we show that CHD8 promotes the association of β-catenin and histone H1, with formation of the trimeric complex on chromatin being required for inhibition of β-catenin-dependent transactivation. A CHD8 mutant that lacks the histone H1 binding domain did not show such inhibitory activity, indicating that histone H1 recruitment is essential for the inhibitory effect of CHD8. Furthermore, either depletion of histone H1 or expression of a dominant negative mutant of this protein resulted in enhancement of the response to Wnt signaling. These observations reveal a new mode of regulation of the Wnt signaling pathway by CHD8, which counteracts β-catenin function through recruitment of histone H1 to Wnt target genes. Given that CHD8 is expressed predominantly during embryogenesis, it may thus contribute to setting a threshold for responsiveness to Wnt signaling that operates in a development-dependent manner.

MeSH Terms
Animals Binding Sites Cell Line DNA-Binding Proteins/chemistry,genetics,metabolism Gene Expression Gene Expression Regulation Histones/genetics,metabolism Humans Mice Mutation Transcription Factors/chemistry,genetics,metabolism Wnt Proteins/genetics,metabolism Wnt Signaling Pathway beta Catenin/genetics,metabolism
Chemicals
CHD8 protein, human DNA-Binding Proteins Histones Transcription Factors Wnt Proteins beta Catenin duplin protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Nishiyama Masaaki
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Skoultchi Arthur I
Nakayama Keiichi I
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.06409-11
Published
2012-01-00
Epub
2011-00-14
Pages
501-12
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC3255766
Subset
IM
Grants
NCI NIH HHS · R01 CA079057 · United States
NCI NIH HHS · R56 CA079057 · United States
NCI NIH HHS · CA79057 · United States
External Links
PubMed source DOI: 10.1128/MCB.06409-11 PMC Full Text View journal details
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