H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription
Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes du...
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| Veröffentlicht in: | Blood 2008-07, Vol.112 (2), p.406-414 |
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| creator | Sawado, Tomoyuki Halow, Jessica Im, Hogune Ragoczy, Tobias Bresnick, Emery H. Bender, M.A. Groudine, Mark |
| description | Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template. |
| doi_str_mv | 10.1182/blood-2007-12-128983 |
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To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2007-12-128983</identifier><identifier>PMID: 18441235</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Blood coagulation. Blood cells ; Fundamental and applied biological sciences. Psychology ; Genomics - methods ; Globins - genetics ; Histones - metabolism ; Liver - cytology ; Liver - embryology ; Locus Control Region - genetics ; Methylation ; Mice ; Mice, Mutant Strains ; Molecular and cellular biology ; Red Cells ; Transcription, Genetic ; Transcriptional Activation</subject><ispartof>Blood, 2008-07, Vol.112 (2), p.406-414</ispartof><rights>2008 American Society of Hematology</rights><rights>2008 INIST-CNRS</rights><rights>2008 by The American Society of Hematology 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3363-2416b58b132c490f804b7ce41872e25af566b11990c8fef33505b9c1d53551cb3</citedby><cites>FETCH-LOGICAL-c3363-2416b58b132c490f804b7ce41872e25af566b11990c8fef33505b9c1d53551cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20499329$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18441235$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sawado, Tomoyuki</creatorcontrib><creatorcontrib>Halow, Jessica</creatorcontrib><creatorcontrib>Im, Hogune</creatorcontrib><creatorcontrib>Ragoczy, Tobias</creatorcontrib><creatorcontrib>Bresnick, Emery H.</creatorcontrib><creatorcontrib>Bender, M.A.</creatorcontrib><creatorcontrib>Groudine, Mark</creatorcontrib><title>H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription</title><title>Blood</title><addtitle>Blood</addtitle><description>Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood coagulation. Blood cells</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genomics - methods</subject><subject>Globins - genetics</subject><subject>Histones - metabolism</subject><subject>Liver - cytology</subject><subject>Liver - embryology</subject><subject>Locus Control Region - genetics</subject><subject>Methylation</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Molecular and cellular biology</subject><subject>Red Cells</subject><subject>Transcription, Genetic</subject><subject>Transcriptional Activation</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd-K1DAUxoMo7rj6BiK50btq_rbNjSDD6ooDguh1SNLTaTRtatIO7LVv5IP4TGacYVdvhEAg53e-fOd8CD2l5CWlLXtlQ4xdxQhpKsrKaVXL76ENlaytCGHkPtoQQupKqIZeoEc5fyWECs7kQ3RBWyEo43KDflxz_KFRuPMjLMNNMIuPEx5N-pZxBwcIcR5hWkzAxi3-cCrHHi8D4F8_q32I1k94DxNguy7YZ5ygWx10eJ0Ludt-qkbovFnKy-D3QxWOonhJZsou-fmo9xg96E3I8OR8X6Ivb68-b6-r3cd377dvdpXjvOYVE7S2srWUMycU6VsibONA0LZhwKTpZV1bSpUiru2h51wSaZWjneRSUmf5JXp90p1XW0y5MlcyQc_Jl3lvdDRe_1uZ_KD38aCZEKyRpAi8OAuk-H2FvOjRZwchmAnimnWtmGqklAUUJ9ClmHOC_vYTSvQxPf0nPX1MT1OmT-mVtmd_G7xrOsdVgOdnwGRnQl-26Hy-5RgRSnGm7iaFss6Dh6Sz8zCVWHwCt-gu-v87-Q0vKrtG</recordid><startdate>20080715</startdate><enddate>20080715</enddate><creator>Sawado, Tomoyuki</creator><creator>Halow, Jessica</creator><creator>Im, Hogune</creator><creator>Ragoczy, Tobias</creator><creator>Bresnick, Emery H.</creator><creator>Bender, M.A.</creator><creator>Groudine, Mark</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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></search><sort><creationdate>20080715</creationdate><title>H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription</title><author>Sawado, Tomoyuki ; Halow, Jessica ; Im, Hogune ; Ragoczy, Tobias ; Bresnick, Emery H. ; Bender, M.A. ; Groudine, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3363-2416b58b132c490f804b7ce41872e25af566b11990c8fef33505b9c1d53551cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood coagulation. Blood cells</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genomics - methods</topic><topic>Globins - genetics</topic><topic>Histones - metabolism</topic><topic>Liver - cytology</topic><topic>Liver - embryology</topic><topic>Locus Control Region - genetics</topic><topic>Methylation</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Molecular and cellular biology</topic><topic>Red Cells</topic><topic>Transcription, Genetic</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sawado, Tomoyuki</creatorcontrib><creatorcontrib>Halow, Jessica</creatorcontrib><creatorcontrib>Im, Hogune</creatorcontrib><creatorcontrib>Ragoczy, Tobias</creatorcontrib><creatorcontrib>Bresnick, Emery H.</creatorcontrib><creatorcontrib>Bender, M.A.</creatorcontrib><creatorcontrib>Groudine, Mark</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sawado, Tomoyuki</au><au>Halow, Jessica</au><au>Im, Hogune</au><au>Ragoczy, Tobias</au><au>Bresnick, Emery H.</au><au>Bender, M.A.</au><au>Groudine, Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2008-07-15</date><risdate>2008</risdate><volume>112</volume><issue>2</issue><spage>406</spage><epage>414</epage><pages>406-414</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>18441235</pmid><doi>10.1182/blood-2007-12-128983</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Blood coagulation. Blood cells Fundamental and applied biological sciences. Psychology Genomics - methods Globins - genetics Histones - metabolism Liver - cytology Liver - embryology Locus Control Region - genetics Methylation Mice Mice, Mutant Strains Molecular and cellular biology Red Cells Transcription, Genetic Transcriptional Activation |
| title | H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription |
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