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We find that a large fraction of the genes that change in expression in the presence of mutant huntingtin demonstrate significant changes in DNA methylation. Regions with low CpG content, which have previously been shown to undergo methylation changes in response to neuronal activity, are disproportionately affected. On the basis of the sequence of regions that change in methylation, we identify AP-1 and SOX2 as transcriptional regulators associated with DNA methylation changes, and we confirm these hypotheses using genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq). Our findings suggest new mechanisms for the effects of polyglutamine-expanded HTT. These results also raise important questions about the potential effects of changes in DNA methylation on neurogenesis and cognitive decline in patients with Huntington disease.<\/jats:p>","DOI":"10.1073\/pnas.1221292110","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T02:27:25Z","timestamp":1358908045000},"page":"2354-2359","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["Extensive changes in DNA methylation are associated with expression of mutant huntingtin"],"prefix":"10.1073","volume":"110","author":[{"given":"Christopher W.","family":"Ng","sequence":"first","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferah","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Sing","family":"Yap","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Dalin","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio J.","family":"Velez","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Labadorf","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Housman","sequence":"additional","affiliation":[{"name":"Biology, Massachusetts Institute of Technology, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Departments of aBiological Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,1,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/hmg\/ddl013","article-title":"Regional and cellular gene expression changes in human Huntington\u2019s disease brain","volume":"15","author":"Hodges A","year":"2006","unstructured":"A Hodges, et al., Regional and cellular gene expression changes in human Huntington\u2019s disease brain. 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