H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction
Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker his...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2020-06, Vol.117 (25), p.14251-14258 |
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| creator | Healton, Sean E. Pinto, Hugo D. Mishra, Laxmi N. Hamilton, Gregory A. Wheat, Justin C. Swist-Rosowska, Kalina Shukeir, Nicholas Dou, Yali Steidl, Ulrich Jenuwein, Thomas Gamble, Matthew J. Skoultchi, Arthur I. |
| description | Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de-repression of several classes of repetitive sequences, including major satellite, LINE-1, and ERV. Activation of repetitive sequence transcription is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant repressive mechanism for silencing of repetitive major satellite sequences. Our findings elucidate two distinct, H1-mediated pathways for silencing heterochromatin. |
| doi_str_mv | 10.1073/pnas.1920725117 |
| format | Article |
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Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de-repression of several classes of repetitive sequences, including major satellite, LINE-1, and ERV. Activation of repetitive sequence transcription is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant repressive mechanism for silencing of repetitive major satellite sequences. Our findings elucidate two distinct, H1-mediated pathways for silencing heterochromatin.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1920725117</identifier><identifier>PMID: 32513732</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biological Sciences ; Chromatin ; Chromatin - metabolism ; Compaction ; Control stability ; Depletion ; DNA methylation ; Embryo cells ; Epigenomics ; Genomes ; Genomic instability ; Heterochromatin ; Heterochromatin - metabolism ; Histone-Lysine N-Methyltransferase - metabolism ; Histones ; Histones - metabolism ; Methylation ; Methyltransferases - metabolism ; Mice ; Mouse Embryonic Stem Cells - metabolism ; Repetitive Sequences, Nucleic Acid - physiology ; Repressor Proteins - metabolism ; Stem cell transplantation ; Stem cells ; Transcription activation</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2020-06, Vol.117 (25), p.14251-14258</ispartof><rights>Copyright National Academy of Sciences Jun 23, 2020</rights><rights>2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-37a714713b1d2f7648c89034a187cf744529cff27aaea54f723a05a6cf94bf1c3</citedby><cites>FETCH-LOGICAL-c509t-37a714713b1d2f7648c89034a187cf744529cff27aaea54f723a05a6cf94bf1c3</cites><orcidid>0000-0003-0018-4981 ; 0000-0003-2506-4185 ; 0000-0002-6970-4693 ; 0000-0002-4040-1429 ; 0000-0002-6596-9651 ; 0000-0002-7864-6958 ; 0000-0002-7844-597X ; 0000-0002-0470-0421 ; 0000-0003-2024-3715 ; 0000-0001-5096-8077</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26934953$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26934953$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32513732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Healton, Sean E.</creatorcontrib><creatorcontrib>Pinto, Hugo D.</creatorcontrib><creatorcontrib>Mishra, Laxmi N.</creatorcontrib><creatorcontrib>Hamilton, Gregory A.</creatorcontrib><creatorcontrib>Wheat, Justin C.</creatorcontrib><creatorcontrib>Swist-Rosowska, Kalina</creatorcontrib><creatorcontrib>Shukeir, Nicholas</creatorcontrib><creatorcontrib>Dou, Yali</creatorcontrib><creatorcontrib>Steidl, Ulrich</creatorcontrib><creatorcontrib>Jenuwein, Thomas</creatorcontrib><creatorcontrib>Gamble, Matthew J.</creatorcontrib><creatorcontrib>Skoultchi, Arthur I.</creatorcontrib><title>H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de-repression of several classes of repetitive sequences, including major satellite, LINE-1, and ERV. Activation of repetitive sequence transcription is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant repressive mechanism for silencing of repetitive major satellite sequences. 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| subjects | Animals Biological Sciences Chromatin Chromatin - metabolism Compaction Control stability Depletion DNA methylation Embryo cells Epigenomics Genomes Genomic instability Heterochromatin Heterochromatin - metabolism Histone-Lysine N-Methyltransferase - metabolism Histones Histones - metabolism Methylation Methyltransferases - metabolism Mice Mouse Embryonic Stem Cells - metabolism Repetitive Sequences, Nucleic Acid - physiology Repressor Proteins - metabolism Stem cell transplantation Stem cells Transcription activation |
| title | H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction |
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