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Although mechanisms of toxicity are poorly delineated, transcriptional dysregulation is a likely contributor. To identify modifiers that act at the level of CAG expansion and\/or downstream pathogenic processes, we tested the impact of genetic knockout, in\n                    <jats:italic>Htt<\/jats:italic>\n                    <jats:sup>Q111<\/jats:sup>\n                    mice, of\n                    <jats:italic>Hdac2<\/jats:italic>\n                    or\n                    <jats:italic>Hdac3<\/jats:italic>\n                    in medium-spiny striatal neurons that exhibit extensive CAG expansion and exquisite disease vulnerability. Both knockouts moderately attenuated CAG expansion, with\n                    <jats:italic>Hdac2<\/jats:italic>\n                    knockout decreasing nuclear huntingtin pathology.\n                    <jats:italic>Hdac2<\/jats:italic>\n                    knockout resulted in a substantial transcriptional response that included modification of transcriptional dysregulation elicited by the\n                    <jats:italic>Htt<\/jats:italic>\n                    <jats:sup>Q111<\/jats:sup>\n                    allele, likely via mechanisms unrelated to instability suppression. Our results identify novel modifiers of different aspects of HD pathogenesis in medium-spiny neurons and highlight a complex relationship between the expanded\n                    <jats:italic>Htt<\/jats:italic>\n                    allele and\n                    <jats:italic>Hdac2<\/jats:italic>\n                    with implications for targeting transcriptional dysregulation in HD.\n                  <\/jats:p>","DOI":"10.7554\/elife.55911","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T10:00:14Z","timestamp":1601373614000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.55911","source":"Crossref","is-referenced-by-count":21,"title":["Histone deacetylase knockouts modify transcription, CAG instability and nuclear pathology in Huntington disease mice"],"prefix":"10.7554","volume":"9","author":[{"given":"Marina","family":"Kovalenko","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-2625","authenticated-orcid":true,"given":"Serkan","family":"Erdin","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa A","family":"Andrew","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"St Claire","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Shaughnessey","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leroy","family":"Hubert","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-158X","authenticated-orcid":true,"given":"Jo\u00e3o Lu\u00eds","family":"Neto","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Stortchevoi","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-8093","authenticated-orcid":true,"given":"Daniel M","family":"Fass","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Mouro Pinto","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7872-168X","authenticated-orcid":true,"given":"Stephen J","family":"Haggarty","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Wilson","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E","family":"Talkowski","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Harvard Medical School, Boston, United States"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, United States"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2619-589X","authenticated-orcid":true,"given":"Vanessa C","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Center for Genomic 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