{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:53:39Z","timestamp":1781110419964,"version":"3.54.1"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"name":"NIH","award":["R01 NS089076"],"award-info":[{"award-number":["R01 NS089076"]}]},{"name":"NIH","award":["P30-ES002109"],"award-info":[{"award-number":["P30-ES002109"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,12,3]]},"abstract":"<jats:p>\n                    Huntington\u2019s disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (\n                    <jats:italic>HTT<\/jats:italic>\n                    ) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27acetylation in the striatum of R6\/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6\/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1908113116","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T16:05:14Z","timestamp":1574179514000},"page":"24840-24851","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington\u2019s disease"],"prefix":"10.1073","volume":"116","author":[{"given":"Ferah","family":"Yildirim","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry, Department of Psychiatry and Psychotherapy, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany;"},{"name":"NeuroCure Cluster of Excellence, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Ng","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Kappes","sequence":"additional","affiliation":[{"name":"Neuroscience Paris Seine-Institut de Biologie Paris-Seine, INSERM UMRS 1130\/CNRS UMR8246, Sorbonne University, Universit\u00e9 Pierre et Marie Curie, 75005 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Ehrenberger","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan K.","family":"Rigby","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Stivanello","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Gipson","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Soltis","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vanhoutte","sequence":"additional","affiliation":[{"name":"Neuroscience Paris Seine-Institut de Biologie Paris-Seine, INSERM UMRS 1130\/CNRS UMR8246, Sorbonne University, Universit\u00e9 Pierre et Marie Curie, 75005 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyne","family":"Caboche","sequence":"additional","affiliation":[{"name":"Neuroscience Paris Seine-Institut de Biologie Paris-Seine, INSERM UMRS 1130\/CNRS UMR8246, Sorbonne University, Universit\u00e9 Pierre et Marie Curie, 75005 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Housman","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.1073\/pnas.1603871113","article-title":"Selective expression of mutant huntingtin during development recapitulates characteristic features of Huntington\u2019s disease","volume":"113","author":"Molero A. 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