Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters
The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add...
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| Veröffentlicht in: | Nature structural & molecular biology 2018-09, Vol.25 (9), p.766-777 |
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| creator | Jansz, Natasha Keniry, Andrew Trussart, Marie Bildsoe, Heidi Beck, Tamara Tonks, Ian D. Mould, Arne W. Hickey, Peter Breslin, Kelsey Iminitoff, Megan Ritchie, Matthew E. McGlinn, Edwina Kay, Graham F. Murphy, James M. Blewitt, Marnie E. |
| description | The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add Smchd1 to the canon of epigenetic proteins required for Hox-gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes that depend on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we found increased short-range interactions and ectopic enhancer activation. In contrast, the inactive X chromosome was transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in short-range interactions. In the inactive X, we observed spreading of trimethylated histone H3 K27 (H3K27me3) domains into regions not normally decorated by this mark. Together, these data suggest that Smchd1 is able to insulate chromatin, thereby limiting access to other chromatin-modifying proteins.
In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes. |
| doi_str_mv | 10.1038/s41594-018-0111-z |
| format | Article |
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In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes.</description><identifier>ISSN: 1545-9993</identifier><identifier>EISSN: 1545-9985</identifier><identifier>DOI: 10.1038/s41594-018-0111-z</identifier><identifier>PMID: 30127357</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>14/63 ; 38/39 ; 38/91 ; 45 ; 631/208/177 ; 631/337/100/101 ; 631/337/176/1433 ; 631/337/176/2016 ; Ablation ; Biochemistry ; Biological Microscopy ; Biomedical and Life Sciences ; Chromatin ; Chromosomes ; DNA sequencing ; Domains ; Epigenetic inheritance ; Gene expression ; Gene regulation ; Genes ; Genetic regulation ; Genomes ; Genomics ; Histone H3 ; Image processing equipment ; Life Sciences ; Membrane Biology ; Novels ; Protein Structure ; Proteins ; Transcription ; X chromosome ; X chromosomes</subject><ispartof>Nature structural & molecular biology, 2018-09, Vol.25 (9), p.766-777</ispartof><rights>The Author(s) 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-96e00e1249d0f122b20710138664779d53452e91187349b6da0c5fdd57ac512f3</citedby><cites>FETCH-LOGICAL-c539t-96e00e1249d0f122b20710138664779d53452e91187349b6da0c5fdd57ac512f3</cites><orcidid>0000-0003-0195-3949 ; 0000-0002-8153-6258 ; 0000-0002-3319-8493 ; 0000-0002-1829-986X ; 0000-0002-2004-4348 ; 0000-0002-2984-1474</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41594-018-0111-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41594-018-0111-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30127357$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jansz, Natasha</creatorcontrib><creatorcontrib>Keniry, Andrew</creatorcontrib><creatorcontrib>Trussart, Marie</creatorcontrib><creatorcontrib>Bildsoe, Heidi</creatorcontrib><creatorcontrib>Beck, Tamara</creatorcontrib><creatorcontrib>Tonks, Ian D.</creatorcontrib><creatorcontrib>Mould, Arne W.</creatorcontrib><creatorcontrib>Hickey, Peter</creatorcontrib><creatorcontrib>Breslin, Kelsey</creatorcontrib><creatorcontrib>Iminitoff, Megan</creatorcontrib><creatorcontrib>Ritchie, Matthew E.</creatorcontrib><creatorcontrib>McGlinn, Edwina</creatorcontrib><creatorcontrib>Kay, Graham F.</creatorcontrib><creatorcontrib>Murphy, James M.</creatorcontrib><creatorcontrib>Blewitt, Marnie E.</creatorcontrib><title>Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters</title><title>Nature structural & molecular biology</title><addtitle>Nat Struct Mol Biol</addtitle><addtitle>Nat Struct Mol Biol</addtitle><description>The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add Smchd1 to the canon of epigenetic proteins required for Hox-gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes that depend on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we found increased short-range interactions and ectopic enhancer activation. In contrast, the inactive X chromosome was transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in short-range interactions. In the inactive X, we observed spreading of trimethylated histone H3 K27 (H3K27me3) domains into regions not normally decorated by this mark. Together, these data suggest that Smchd1 is able to insulate chromatin, thereby limiting access to other chromatin-modifying proteins.
In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes.</description><subject>14/63</subject><subject>38/39</subject><subject>38/91</subject><subject>45</subject><subject>631/208/177</subject><subject>631/337/100/101</subject><subject>631/337/176/1433</subject><subject>631/337/176/2016</subject><subject>Ablation</subject><subject>Biochemistry</subject><subject>Biological Microscopy</subject><subject>Biomedical and Life Sciences</subject><subject>Chromatin</subject><subject>Chromosomes</subject><subject>DNA sequencing</subject><subject>Domains</subject><subject>Epigenetic inheritance</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic regulation</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Histone 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E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters</atitle><jtitle>Nature structural & molecular biology</jtitle><stitle>Nat Struct Mol Biol</stitle><addtitle>Nat Struct Mol Biol</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>25</volume><issue>9</issue><spage>766</spage><epage>777</epage><pages>766-777</pages><issn>1545-9993</issn><eissn>1545-9985</eissn><abstract>The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add Smchd1 to the canon of epigenetic proteins required for Hox-gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes that depend on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we found increased short-range interactions and ectopic enhancer activation. In contrast, the inactive X chromosome was transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in short-range interactions. In the inactive X, we observed spreading of trimethylated histone H3 K27 (H3K27me3) domains into regions not normally decorated by this mark. Together, these data suggest that Smchd1 is able to insulate chromatin, thereby limiting access to other chromatin-modifying proteins.
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| subjects | 14/63 38/39 38/91 45 631/208/177 631/337/100/101 631/337/176/1433 631/337/176/2016 Ablation Biochemistry Biological Microscopy Biomedical and Life Sciences Chromatin Chromosomes DNA sequencing Domains Epigenetic inheritance Gene expression Gene regulation Genes Genetic regulation Genomes Genomics Histone H3 Image processing equipment Life Sciences Membrane Biology Novels Protein Structure Proteins Transcription X chromosome X chromosomes |
| title | Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters |
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