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Under normal conditions, the CREB Binding Protein interacts with CREB elements and acetylates Lysine 27 of Histone 3 to direct the expression of several genes. However, mutant Htt causes depletion of CBP, which in turn induces altered histone acetylation patterns and transcriptional deregulation. Here, we have studied a differential expression analysis and H3K27ac variation in 4- and 6-week-old R6\/2 mice as a model of juvenile HD. The analysis of differential gene expression and acetylation levels were integrated into Gene Regulatory Networks revealing key regulators involved in the altered transcription cascade. Our results show changes in acetylation and gene expression levels that are related to impaired neuronal development, and key regulators clearly defined in 6-week-old mice are proposed to drive the downstream regulatory cascade in HD. Here, we describe the first approach to determine the relationship among epigenetic changes in the early stages of HD. We determined the existence of changes in pre-symptomatic stages of HD as a starting point for early onset indicators of the progression of this disease.<\/jats:p>","DOI":"10.3390\/ijms241310848","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:43:30Z","timestamp":1688085810000},"page":"10848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptional and Histone Acetylation Changes Associated with CRE Elements Expose Key Factors Governing the Regulatory Circuit in the Early Stage of Huntington\u2019s Disease Models"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-9230","authenticated-orcid":false,"given":"Sandra","family":"Arancibia-Opazo","sequence":"first","affiliation":[{"name":"Chromatin, Epigenetic, and Neuroscience Laboratory, Centro de Gen\u00f3mica y Bioinform\u00e1tica, Facultad de Ciencias, Ingenier\u00eda y Tecnolog\u00eda, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Programa de Doctorado en Gen\u00f3mica Integrativa, Vicerrector\u00eda de Investigaci\u00f3n, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Laboratorio de Redes Biol\u00f3gicas, Centro Cient\u00edfico y Tecnol\u00f3gico de Excelencia Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Universidad San Sebasti\u00e1n, Santiago 8580704, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Sebasti\u00e1n","family":"Contreras-Riquelme","sequence":"additional","affiliation":[{"name":"Plant Genome Regulation Lab, Centro de Biotecnolog\u00eda Vegetal, Facultad de Ciencias de la Vida, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-9930","authenticated-orcid":false,"given":"Mario","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Chromatin, Epigenetic, and Neuroscience Laboratory, Centro de Gen\u00f3mica y Bioinform\u00e1tica, Facultad de Ciencias, Ingenier\u00eda y Tecnolog\u00eda, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisol","family":"Cisternas-Olmedo","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Integrativa, Facultad de Ciencias, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Biomedical Neuroscience Institute, University of Chile, Santiago 8380455, Chile"},{"name":"Center for Geroscience, Brain Health, and Metabolism, Santiago 8380453, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4305-7387","authenticated-orcid":false,"given":"Ren\u00e9 L.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Integrativa, Facultad de Ciencias, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Biomedical Neuroscience Institute, University of Chile, Santiago 8380455, Chile"},{"name":"Center for Geroscience, Brain Health, and Metabolism, Santiago 8380453, Chile"},{"name":"Escuela de Biotecnolog\u00eda, Facultad de Ciencias, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-3325","authenticated-orcid":false,"given":"Alberto J. M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratorio de Redes Biol\u00f3gicas, Centro Cient\u00edfico y Tecnol\u00f3gico de Excelencia Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Universidad San Sebasti\u00e1n, Santiago 8580704, Chile"},{"name":"Escuela de Ingenier\u00eda, Facultad de Ingenier\u00eda, Arquitectura y Dise\u00f1o, Universidad San Sebasti\u00e1n, Santiago 7500000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-7628","authenticated-orcid":false,"given":"Mauricio A.","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"Chromatin, Epigenetic, and Neuroscience Laboratory, Centro de Gen\u00f3mica y Bioinform\u00e1tica, Facultad de Ciencias, Ingenier\u00eda y Tecnolog\u00eda, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Centro de Oncolog\u00eda de Precisi\u00f3n, Facultad de Medicina Universidad Mayor, Santiago 7560908, Chile"},{"name":"Laboratorio de Investigaci\u00f3n en Salud de Precisi\u00f3n, Departamento de Procesos Diagn\u00f3sticos y Evaluaci\u00f3n, Facultad de Ciencias de la Salud, Universidad Cat\u00f3lica de Temuco, Temuco 4813302, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-59259-963-9_2","article-title":"Nontraditional inheritance","volume":"39","author":"McCandless","year":"2006","journal-title":"Princ. 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