A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin
G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the majority of histone H3 lysine 9 mono- and di-methylation (H3K9me1/me2). Widely interspaced zinc finger (WIZ) associates with the G9a-GLP protein complex, but its role in mediating lysine methylation is poo...
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| Veröffentlicht in: | The Journal of biological chemistry 2015-10, Vol.290 (43), p.26088-26102 |
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| container_issue | 43 |
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| container_title | The Journal of biological chemistry |
| container_volume | 290 |
| creator | Simon, Jeremy M. Parker, Joel S. Liu, Feng Rothbart, Scott B. Ait-Si-Ali, Slimane Strahl, Brian D. Jin, Jian Davis, Ian J. Mosley, Amber L. Pattenden, Samantha G. |
| description | G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the majority of histone H3 lysine 9 mono- and di-methylation (H3K9me1/me2). Widely interspaced zinc finger (WIZ) associates with the G9a-GLP protein complex, but its role in mediating lysine methylation is poorly defined. Here, we show that WIZ regulates global H3K9me2 levels by facilitating the interaction of G9a with chromatin. Disrupting the association of G9a-GLP with chromatin by depleting WIZ resulted in altered gene expression and protein-protein interactions that were distinguishable from that of small molecule-based inhibition of G9a/GLP, supporting discrete functions of the G9a-GLP-WIZ chromatin complex in addition to H3K9me2 methylation.
Background: G9a-GLP lysine methyltransferases mono- and di-methylate histone H3 lysine 9 (H3K9me2).
Results: Widely interspaced zinc finger (WIZ) regulates H3K9me2 levels through a mechanism that involves retention of G9a on chromatin.
Conclusion: The G9a-GLP-WIZ complex has unique functions when bound to chromatin that are independent of the H3K9me2 mark.
Significance: Combining pharmacologic and genetic manipulations is essential to any translational hypotheses related to G9a function. |
| doi_str_mv | 10.1074/jbc.M115.654459 |
| format | Article |
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Background: G9a-GLP lysine methyltransferases mono- and di-methylate histone H3 lysine 9 (H3K9me2).
Results: Widely interspaced zinc finger (WIZ) regulates H3K9me2 levels through a mechanism that involves retention of G9a on chromatin.
Conclusion: The G9a-GLP-WIZ complex has unique functions when bound to chromatin that are independent of the H3K9me2 mark.
Significance: Combining pharmacologic and genetic manipulations is essential to any translational hypotheses related to G9a function.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M115.654459</identifier><identifier>PMID: 26338712</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Chromatin - metabolism ; Chromatin Immunoprecipitation ; chromatin modification ; chromatin regulation ; DNA Methylation ; Gene Expression - genetics ; Gene Knockdown Techniques ; Gene Regulation ; HEK293 Cells ; HeLa Cells ; Humans ; Kruppel-Like Transcription Factors - genetics ; Kruppel-Like Transcription Factors - physiology ; Life Sciences ; Methyltransferases - metabolism ; Protein Binding ; protein methylation ; transcription ; transcription coregulator</subject><ispartof>The Journal of biological chemistry, 2015-10, Vol.290 (43), p.26088-26102</ispartof><rights>2015 © 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2015 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2015 by The American Society for Biochemistry and Molecular Biology, Inc. 2015 The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-cfa80bcbd67a2d0b8320bf59494da417e5ebfe8cc51e50fb1fab1abb8047d4a73</citedby><cites>FETCH-LOGICAL-c543t-cfa80bcbd67a2d0b8320bf59494da417e5ebfe8cc51e50fb1fab1abb8047d4a73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646261/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646261/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26338712$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03051615$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Simon, Jeremy M.</creatorcontrib><creatorcontrib>Parker, Joel S.</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Rothbart, Scott B.</creatorcontrib><creatorcontrib>Ait-Si-Ali, Slimane</creatorcontrib><creatorcontrib>Strahl, Brian D.</creatorcontrib><creatorcontrib>Jin, Jian</creatorcontrib><creatorcontrib>Davis, Ian J.</creatorcontrib><creatorcontrib>Mosley, Amber L.</creatorcontrib><creatorcontrib>Pattenden, Samantha G.</creatorcontrib><title>A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the majority of histone H3 lysine 9 mono- and di-methylation (H3K9me1/me2). Widely interspaced zinc finger (WIZ) associates with the G9a-GLP protein complex, but its role in mediating lysine methylation is poorly defined. Here, we show that WIZ regulates global H3K9me2 levels by facilitating the interaction of G9a with chromatin. Disrupting the association of G9a-GLP with chromatin by depleting WIZ resulted in altered gene expression and protein-protein interactions that were distinguishable from that of small molecule-based inhibition of G9a/GLP, supporting discrete functions of the G9a-GLP-WIZ chromatin complex in addition to H3K9me2 methylation.
Background: G9a-GLP lysine methyltransferases mono- and di-methylate histone H3 lysine 9 (H3K9me2).
Results: Widely interspaced zinc finger (WIZ) regulates H3K9me2 levels through a mechanism that involves retention of G9a on chromatin.
Conclusion: The G9a-GLP-WIZ complex has unique functions when bound to chromatin that are independent of the H3K9me2 mark.
Significance: Combining pharmacologic and genetic manipulations is essential to any translational hypotheses related to G9a function.</description><subject>Chromatin - metabolism</subject><subject>Chromatin Immunoprecipitation</subject><subject>chromatin modification</subject><subject>chromatin regulation</subject><subject>DNA Methylation</subject><subject>Gene Expression - genetics</subject><subject>Gene Knockdown Techniques</subject><subject>Gene Regulation</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Kruppel-Like Transcription Factors - physiology</subject><subject>Life Sciences</subject><subject>Methyltransferases - metabolism</subject><subject>Protein Binding</subject><subject>protein methylation</subject><subject>transcription</subject><subject>transcription coregulator</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1rHCEYh6W0NNu0596Cx-YwG53R-bgEliUfCxsKoSUlF1HnNWOY1UXNwv73dZkkNIF6EXyf348XH4S-UzKnpGFnj0rPbyjl85ozxrsPaEZJWxUVp38-ohkhJS26krdH6EuMjyQf1tHP6Kisq6ptaDlDZoFv_QjY-IDvbA_jHq9cghC3UkOP763T-NK6Bwj4x93q_hRbh28hgUvWO-wNTgPgq07iG0jDfkxBumggyAg4z5dD8BuZrPuKPhk5Rvj2fB-j35cXv5bXxfrn1Wq5WBeasyoV2siWKK36upFlT1RblUQZ3rGO9ZLRBjgoA63WnAInRlEjFZVKtYQ1PZNNdYzOp97tk9pAr_OeQY5iG-xGhr3w0oq3E2cH8eB3gtWsLmuaC06nguFd7HqxFoc3UhFOa8p3B_ZsYnXwMQYwrwFKxEGPyHrEQY-Y9OTEyb_rvfIvPjLQTQDkT9pZCCJqCy6rsAF0Er23_y3_Cy9ToDI</recordid><startdate>20151023</startdate><enddate>20151023</enddate><creator>Simon, Jeremy M.</creator><creator>Parker, Joel S.</creator><creator>Liu, Feng</creator><creator>Rothbart, Scott B.</creator><creator>Ait-Si-Ali, Slimane</creator><creator>Strahl, Brian D.</creator><creator>Jin, Jian</creator><creator>Davis, Ian J.</creator><creator>Mosley, Amber L.</creator><creator>Pattenden, Samantha G.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>1XC</scope><scope>5PM</scope></search><sort><creationdate>20151023</creationdate><title>A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin</title><author>Simon, Jeremy M. ; Parker, Joel S. ; Liu, Feng ; Rothbart, Scott B. ; Ait-Si-Ali, Slimane ; Strahl, Brian D. ; Jin, Jian ; Davis, Ian J. ; Mosley, Amber L. ; Pattenden, Samantha G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c543t-cfa80bcbd67a2d0b8320bf59494da417e5ebfe8cc51e50fb1fab1abb8047d4a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Chromatin - metabolism</topic><topic>Chromatin Immunoprecipitation</topic><topic>chromatin modification</topic><topic>chromatin regulation</topic><topic>DNA Methylation</topic><topic>Gene Expression - genetics</topic><topic>Gene Knockdown Techniques</topic><topic>Gene Regulation</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Kruppel-Like Transcription Factors - physiology</topic><topic>Life Sciences</topic><topic>Methyltransferases - metabolism</topic><topic>Protein Binding</topic><topic>protein methylation</topic><topic>transcription</topic><topic>transcription coregulator</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Simon, Jeremy M.</creatorcontrib><creatorcontrib>Parker, Joel S.</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Rothbart, Scott B.</creatorcontrib><creatorcontrib>Ait-Si-Ali, Slimane</creatorcontrib><creatorcontrib>Strahl, Brian D.</creatorcontrib><creatorcontrib>Jin, Jian</creatorcontrib><creatorcontrib>Davis, Ian J.</creatorcontrib><creatorcontrib>Mosley, Amber L.</creatorcontrib><creatorcontrib>Pattenden, Samantha G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Simon, Jeremy M.</au><au>Parker, Joel S.</au><au>Liu, Feng</au><au>Rothbart, Scott B.</au><au>Ait-Si-Ali, Slimane</au><au>Strahl, Brian D.</au><au>Jin, Jian</au><au>Davis, Ian J.</au><au>Mosley, Amber L.</au><au>Pattenden, Samantha G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2015-10-23</date><risdate>2015</risdate><volume>290</volume><issue>43</issue><spage>26088</spage><epage>26102</epage><pages>26088-26102</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the majority of histone H3 lysine 9 mono- and di-methylation (H3K9me1/me2). Widely interspaced zinc finger (WIZ) associates with the G9a-GLP protein complex, but its role in mediating lysine methylation is poorly defined. Here, we show that WIZ regulates global H3K9me2 levels by facilitating the interaction of G9a with chromatin. Disrupting the association of G9a-GLP with chromatin by depleting WIZ resulted in altered gene expression and protein-protein interactions that were distinguishable from that of small molecule-based inhibition of G9a/GLP, supporting discrete functions of the G9a-GLP-WIZ chromatin complex in addition to H3K9me2 methylation.
Background: G9a-GLP lysine methyltransferases mono- and di-methylate histone H3 lysine 9 (H3K9me2).
Results: Widely interspaced zinc finger (WIZ) regulates H3K9me2 levels through a mechanism that involves retention of G9a on chromatin.
Conclusion: The G9a-GLP-WIZ complex has unique functions when bound to chromatin that are independent of the H3K9me2 mark.
Significance: Combining pharmacologic and genetic manipulations is essential to any translational hypotheses related to G9a function.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26338712</pmid><doi>10.1074/jbc.M115.654459</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Chromatin - metabolism Chromatin Immunoprecipitation chromatin modification chromatin regulation DNA Methylation Gene Expression - genetics Gene Knockdown Techniques Gene Regulation HEK293 Cells HeLa Cells Humans Kruppel-Like Transcription Factors - genetics Kruppel-Like Transcription Factors - physiology Life Sciences Methyltransferases - metabolism Protein Binding protein methylation transcription transcription coregulator |
| title | A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin |
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