H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation

Seung Min Yang, Byung Ju Kim, Laura Norwood Toro, Arthur I. Skoultchi

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Epigenetic silencing in mammals involves DNA methylation and posttranslational modifications of core histones. Here we show that the H1 linker histone plays a key role in regulating both DNA methylation and histone H3 methylation at the H19 and Gtl2 loci in mouse ES cells. Some, but not all, murine H1 subtypes interact with DNA methyltransferases DNMT1 and DNMT3B. The interactions are direct and require a portion of the H1 C-terminal domain. Expression of an H1 subtype that interacts with DNMT1 and DNMT3B in ES cells leads to their recruitment and DNA methylation of the H19 and Gtl2 imprinting control regions. H1 also interferes with binding of the SET7/9 histone methyltransferase to the imprinting control regions, inhibiting production of an activating methylation mark on histone H3 lysine 4. H1-dependent recruitment of DNMT1 and DNMT3B and interference with the binding of SET7/9 also were observed with chromatin reconstituted in vitro. The data support a model in which H1 plays anactive rolein helping direct two processes that leadtothe formation of epigenetic silencing marks. The data also provide evidence for functional differences among the H1 subtypes expressed in somatic mammalian cells.

Original languageEnglish (US)
Pages (from-to)1708-1713
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number5
DOIs
StatePublished - Jan 29 2013

Keywords

  • H1 histone triple knockout
  • Mouse embryonic stem cell

ASJC Scopus subject areas

  • General

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