title: H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation.
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 an active role in helping direct two processes that lead to the formation of epigenetic silencing marks. The data also provide evidence for functional differences among the H1 subtypes expressed in somatic mammalian cells.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Yang
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Kim
authors.forename: Laura
authors.initials: L
authors.lastname: Norwood Toro
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Skoultchi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015870:Gene Expression; D018392:Genomic Imprinting / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097584:DNA Methyltransferase 3B
chemical_list: D002843:Chromatin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D020033:Protein Isoforms; D062085:RNA, Long Noncoding; D000097584:DNA Methyltransferase 3B; C094335:H19 long non-coding RNA; C422882:MEG3 non-coding RNA, mouse; C000619381:Dnmt1 protein, mouse