5-hydroxymethylcytosine and gene activity in mouse intestinal differentiation
Cytosine hydroxymethylation (5hmC) in mammalian DNA is the product of oxidation of methylated cytosines (5mC) by Ten-Eleven-Translocation (TET) enzymes. While it has been shown that the TETs influence 5mC metabolism, pluripotency and differentiation during early embryonic development, the functional...
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| Veröffentlicht in: | Scientific reports 2020-01, Vol.10 (1), p.546-546, Article 546 |
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| description | Cytosine hydroxymethylation (5hmC) in mammalian DNA is the product of oxidation of methylated cytosines (5mC) by Ten-Eleven-Translocation (TET) enzymes. While it has been shown that the TETs influence 5mC metabolism, pluripotency and differentiation during early embryonic development, the functional relationship between gene expression and 5hmC in adult (somatic) stem cell differentiation is still unknown. Here we report that 5hmC levels undergo highly dynamic changes during adult stem cell differentiation from intestinal progenitors to differentiated intestinal epithelium. We profiled 5hmC and gene activity in purified mouse intestinal progenitors and differentiated progeny to identify 43425 differentially hydroxymethylated regions and 5325 differentially expressed genes. These differentially marked regions showed both losses and gains of 5hmC after differentiation, despite lower global levels of 5hmC in progenitor cells. In progenitors, 5hmC did not correlate with gene transcript levels, however, upon differentiation the global increase in 5hmC content showed an overall positive correlation with gene expression level as well as prominent associations with histone modifications that typify active genes and enhancer elements. Our data support a gene regulatory role for 5hmC that is predominant over its role in controlling DNA methylation states. |
| doi_str_mv | 10.1038/s41598-019-57214-z |
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We profiled 5hmC and gene activity in purified mouse intestinal progenitors and differentiated progeny to identify 43425 differentially hydroxymethylated regions and 5325 differentially expressed genes. These differentially marked regions showed both losses and gains of 5hmC after differentiation, despite lower global levels of 5hmC in progenitor cells. In progenitors, 5hmC did not correlate with gene transcript levels, however, upon differentiation the global increase in 5hmC content showed an overall positive correlation with gene expression level as well as prominent associations with histone modifications that typify active genes and enhancer elements. Our data support a gene regulatory role for 5hmC that is predominant over its role in controlling DNA methylation states.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-57214-z</identifier><identifier>PMID: 31953501</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/31 ; 38 ; 38/91 ; 45/15 ; 45/91 ; 5-Methylcytosine - analogs & derivatives ; 5-Methylcytosine - pharmacology ; 631/136/142 ; 631/208/176/1988 ; 64/60 ; Adult Stem Cells - cytology ; Adult Stem Cells - drug effects ; Animals ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Differentiation - genetics ; Cytosine ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Embryogenesis ; Embryonic growth stage ; Epithelium ; Gene expression ; Humanities and Social Sciences ; Intestine ; Intestines - cytology ; Mice ; multidisciplinary ; Oxidation ; Pluripotency ; Progenitor cells ; Science ; Science (multidisciplinary) ; Stem cells ; Transcription ; Translocation</subject><ispartof>Scientific reports, 2020-01, Vol.10 (1), p.546-546, Article 546</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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A.</creatorcontrib><creatorcontrib>Murrell, Adele</creatorcontrib><title>5-hydroxymethylcytosine and gene activity in mouse intestinal differentiation</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Cytosine hydroxymethylation (5hmC) in mammalian DNA is the product of oxidation of methylated cytosines (5mC) by Ten-Eleven-Translocation (TET) enzymes. While it has been shown that the TETs influence 5mC metabolism, pluripotency and differentiation during early embryonic development, the functional relationship between gene expression and 5hmC in adult (somatic) stem cell differentiation is still unknown. Here we report that 5hmC levels undergo highly dynamic changes during adult stem cell differentiation from intestinal progenitors to differentiated intestinal epithelium. We profiled 5hmC and gene activity in purified mouse intestinal progenitors and differentiated progeny to identify 43425 differentially hydroxymethylated regions and 5325 differentially expressed genes. These differentially marked regions showed both losses and gains of 5hmC after differentiation, despite lower global levels of 5hmC in progenitor cells. In progenitors, 5hmC did not correlate with gene transcript levels, however, upon differentiation the global increase in 5hmC content showed an overall positive correlation with gene expression level as well as prominent associations with histone modifications that typify active genes and enhancer elements. Our data support a gene regulatory role for 5hmC that is predominant over its role in controlling DNA methylation states.</description><subject>13/100</subject><subject>13/31</subject><subject>38</subject><subject>38/91</subject><subject>45/15</subject><subject>45/91</subject><subject>5-Methylcytosine - analogs & derivatives</subject><subject>5-Methylcytosine - pharmacology</subject><subject>631/136/142</subject><subject>631/208/176/1988</subject><subject>64/60</subject><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - drug effects</subject><subject>Animals</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cytosine</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Epithelium</subject><subject>Gene expression</subject><subject>Humanities and Social Sciences</subject><subject>Intestine</subject><subject>Intestines - cytology</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Oxidation</subject><subject>Pluripotency</subject><subject>Progenitor cells</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Translocation</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UcFO3DAUtCqqgrb8QA9VpF64BPzsPG98QapQC0hUvbRnyyQvu0aJDbYXNXx9vSwF2kN98Uhv3rwZDWMfgB8Dl-1JagB1W3PQNS4FNPXDG3YgeIO1kELsvcL77DClG14eCt2Afsf2JWiUyOGAfcN6Pfcx_Jonyut57OYckvNUWd9XK9qCLrt7l-fK-WoKm0QFZErZeTtWvRsGiuSzs9kF_569HeyY6PDpX7CfX7_8OLuor76fX559vqo7XC5zPVDLVQOSK4EAnSJstLWg9YCtBtGKnstBDL2SvEUpFfSWhEK4JupAYisX7HSne7u5nqjvioFoR3Mb3WTjbIJ15u-Jd2uzCvdGaaU56iJw9CQQw92mpDGTSx2No_VUMhohG1B8ub2-YJ_-od6ETSzhH1miBUS-dSR2rC6GlCINz2aAm21hZleYKYWZx8LMQ1n6-DrG88qfegpB7gipjPyK4svt_8j-BpKJofk</recordid><startdate>20200117</startdate><enddate>20200117</enddate><creator>Uribe-Lewis, Santiago</creator><creator>Carroll, Thomas</creator><creator>Menon, Suraj</creator><creator>Nicholson, Anna</creator><creator>Manasterski, Piotr J.</creator><creator>Winton, Douglas J.</creator><creator>Buczacki, Simon J. 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A.</au><au>Murrell, Adele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5-hydroxymethylcytosine and gene activity in mouse intestinal differentiation</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-01-17</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>546</spage><epage>546</epage><pages>546-546</pages><artnum>546</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Cytosine hydroxymethylation (5hmC) in mammalian DNA is the product of oxidation of methylated cytosines (5mC) by Ten-Eleven-Translocation (TET) enzymes. While it has been shown that the TETs influence 5mC metabolism, pluripotency and differentiation during early embryonic development, the functional relationship between gene expression and 5hmC in adult (somatic) stem cell differentiation is still unknown. Here we report that 5hmC levels undergo highly dynamic changes during adult stem cell differentiation from intestinal progenitors to differentiated intestinal epithelium. We profiled 5hmC and gene activity in purified mouse intestinal progenitors and differentiated progeny to identify 43425 differentially hydroxymethylated regions and 5325 differentially expressed genes. These differentially marked regions showed both losses and gains of 5hmC after differentiation, despite lower global levels of 5hmC in progenitor cells. In progenitors, 5hmC did not correlate with gene transcript levels, however, upon differentiation the global increase in 5hmC content showed an overall positive correlation with gene expression level as well as prominent associations with histone modifications that typify active genes and enhancer elements. Our data support a gene regulatory role for 5hmC that is predominant over its role in controlling DNA methylation states.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31953501</pmid><doi>10.1038/s41598-019-57214-z</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/100 13/31 38 38/91 45/15 45/91 5-Methylcytosine - analogs & derivatives 5-Methylcytosine - pharmacology 631/136/142 631/208/176/1988 64/60 Adult Stem Cells - cytology Adult Stem Cells - drug effects Animals Cell differentiation Cell Differentiation - drug effects Cell Differentiation - genetics Cytosine Deoxyribonucleic acid DNA DNA methylation Embryogenesis Embryonic growth stage Epithelium Gene expression Humanities and Social Sciences Intestine Intestines - cytology Mice multidisciplinary Oxidation Pluripotency Progenitor cells Science Science (multidisciplinary) Stem cells Transcription Translocation |
| title | 5-hydroxymethylcytosine and gene activity in mouse intestinal differentiation |
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