m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin
Abstract Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear...
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creator | Duda, Katarzyna J Ching, Reagan W Jerabek, Lisa Shukeir, Nicholas Erikson, Galina Engist, Bettina Onishi-Seebacher, Megumi Perrera, Valentina Richter, Florian Mittler, Gerhard Fritz, Katharina Helm, Mark Knuckles, Philip Bühler, Marc Jenuwein, Thomas |
description | Abstract
Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin. |
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Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin.</description><identifier>ISSN: 0305-1048</identifier><identifier>ISSN: 1362-4962</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkab364</identifier><identifier>PMID: 33999208</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - metabolism ; Animals ; DNA - metabolism ; Gene regulation, Chromatin and Epigenetics ; Heterochromatin ; Methylation ; Mice ; Mouse Embryonic Stem Cells ; RNA - metabolism ; Tandem Repeat Sequences</subject><ispartof>Nucleic acids research, 2021-06, Vol.49 (10), p.5568-5587</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-95304a6f959c932aaa95dd41ae09e767ae4aafdbc10956a44fc4ffa9097fa163</citedby><cites>FETCH-LOGICAL-c412t-95304a6f959c932aaa95dd41ae09e767ae4aafdbc10956a44fc4ffa9097fa163</cites><orcidid>0000-0001-6661-9795 ; 0000-0002-5256-2641 ; 0000-0002-0154-0928</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191757/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191757/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1603,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33999208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duda, Katarzyna J</creatorcontrib><creatorcontrib>Ching, Reagan W</creatorcontrib><creatorcontrib>Jerabek, Lisa</creatorcontrib><creatorcontrib>Shukeir, Nicholas</creatorcontrib><creatorcontrib>Erikson, Galina</creatorcontrib><creatorcontrib>Engist, Bettina</creatorcontrib><creatorcontrib>Onishi-Seebacher, Megumi</creatorcontrib><creatorcontrib>Perrera, Valentina</creatorcontrib><creatorcontrib>Richter, Florian</creatorcontrib><creatorcontrib>Mittler, Gerhard</creatorcontrib><creatorcontrib>Fritz, Katharina</creatorcontrib><creatorcontrib>Helm, Mark</creatorcontrib><creatorcontrib>Knuckles, Philip</creatorcontrib><creatorcontrib>Bühler, Marc</creatorcontrib><creatorcontrib>Jenuwein, Thomas</creatorcontrib><title>m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Abstract
Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - metabolism</subject><subject>Animals</subject><subject>DNA - metabolism</subject><subject>Gene regulation, Chromatin and Epigenetics</subject><subject>Heterochromatin</subject><subject>Methylation</subject><subject>Mice</subject><subject>Mouse Embryonic Stem Cells</subject><subject>RNA - metabolism</subject><subject>Tandem Repeat Sequences</subject><issn>0305-1048</issn><issn>1362-4962</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAURi1ERYfCij3yCiGhUDt2kjGLSqPyV6kCCXVv3XGuG5c4DrYHaR6DN66rDCPYdOXFd3zsez9CXnH2njMlzieI57c_YSta-YSsuGjrSqq2fkpWTLCm4kyuT8nzlO4Y45I38hk5FUIpVbP1ivzx7Yb--LahHvOwHyG7MNFgqYe7EGmCjOPoMtKIM0KmOcKUTHRzTtSCcSUrSKJmiMGXyxOFlIJxiwem_sH94WPxD_ttdD21IfolLKwPu4R0wIwxHA0vyImFMeHLw3lGbj5_urn8Wl1__3J1ubmujOR1rlQjmITWqkYZJWoAUE3fSw7IFHZtBygBbL81ZUdNC1JaI60FxVRngbfijFws2nm39dgbnMpso56j8xD3OoDT_yeTG_Rt-K3XXPGu6Yrg7UEQw68dpqy9S6asCyYsc-m6qddSSMFFQd8tqIkhpYj2-Axn-qFDXTrUhw4L_frfnx3Zv6UV4M0ChN38qOkeSFmq2w</recordid><startdate>20210604</startdate><enddate>20210604</enddate><creator>Duda, Katarzyna J</creator><creator>Ching, Reagan W</creator><creator>Jerabek, Lisa</creator><creator>Shukeir, Nicholas</creator><creator>Erikson, Galina</creator><creator>Engist, Bettina</creator><creator>Onishi-Seebacher, Megumi</creator><creator>Perrera, Valentina</creator><creator>Richter, Florian</creator><creator>Mittler, Gerhard</creator><creator>Fritz, Katharina</creator><creator>Helm, Mark</creator><creator>Knuckles, Philip</creator><creator>Bühler, Marc</creator><creator>Jenuwein, Thomas</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6661-9795</orcidid><orcidid>https://orcid.org/0000-0002-5256-2641</orcidid><orcidid>https://orcid.org/0000-0002-0154-0928</orcidid></search><sort><creationdate>20210604</creationdate><title>m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin</title><author>Duda, Katarzyna J ; Ching, Reagan W ; Jerabek, Lisa ; Shukeir, Nicholas ; Erikson, Galina ; Engist, Bettina ; Onishi-Seebacher, Megumi ; Perrera, Valentina ; Richter, Florian ; Mittler, Gerhard ; Fritz, Katharina ; Helm, Mark ; Knuckles, Philip ; Bühler, Marc ; Jenuwein, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-95304a6f959c932aaa95dd41ae09e767ae4aafdbc10956a44fc4ffa9097fa163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - metabolism</topic><topic>Animals</topic><topic>DNA - metabolism</topic><topic>Gene regulation, Chromatin and Epigenetics</topic><topic>Heterochromatin</topic><topic>Methylation</topic><topic>Mice</topic><topic>Mouse Embryonic Stem Cells</topic><topic>RNA - metabolism</topic><topic>Tandem Repeat Sequences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duda, Katarzyna J</creatorcontrib><creatorcontrib>Ching, Reagan W</creatorcontrib><creatorcontrib>Jerabek, Lisa</creatorcontrib><creatorcontrib>Shukeir, Nicholas</creatorcontrib><creatorcontrib>Erikson, Galina</creatorcontrib><creatorcontrib>Engist, Bettina</creatorcontrib><creatorcontrib>Onishi-Seebacher, Megumi</creatorcontrib><creatorcontrib>Perrera, Valentina</creatorcontrib><creatorcontrib>Richter, Florian</creatorcontrib><creatorcontrib>Mittler, Gerhard</creatorcontrib><creatorcontrib>Fritz, Katharina</creatorcontrib><creatorcontrib>Helm, Mark</creatorcontrib><creatorcontrib>Knuckles, Philip</creatorcontrib><creatorcontrib>Bühler, Marc</creatorcontrib><creatorcontrib>Jenuwein, Thomas</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duda, Katarzyna J</au><au>Ching, Reagan W</au><au>Jerabek, Lisa</au><au>Shukeir, Nicholas</au><au>Erikson, Galina</au><au>Engist, Bettina</au><au>Onishi-Seebacher, Megumi</au><au>Perrera, Valentina</au><au>Richter, Florian</au><au>Mittler, Gerhard</au><au>Fritz, Katharina</au><au>Helm, Mark</au><au>Knuckles, Philip</au><au>Bühler, Marc</au><au>Jenuwein, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2021-06-04</date><risdate>2021</risdate><volume>49</volume><issue>10</issue><spage>5568</spage><epage>5587</epage><pages>5568-5587</pages><issn>0305-1048</issn><issn>1362-4962</issn><eissn>1362-4962</eissn><abstract>Abstract
Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33999208</pmid><doi>10.1093/nar/gkab364</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0001-6661-9795</orcidid><orcidid>https://orcid.org/0000-0002-5256-2641</orcidid><orcidid>https://orcid.org/0000-0002-0154-0928</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adenosine - analogs & derivatives Adenosine - metabolism Animals DNA - metabolism Gene regulation, Chromatin and Epigenetics Heterochromatin Methylation Mice Mouse Embryonic Stem Cells RNA - metabolism Tandem Repeat Sequences |
title | m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin |
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