Transcriptional and Histone acetylation changes associated with CRE elements expose key factors governing the regulatory circuit in early stage of Huntington’s disease models
Transcriptional and Histone acetylation changes associated with CRE elements expose key factors governing the regulatory circuit in early stage of Huntington’s disease models
Abstract Huntington’s disease (HD) is a disorder caused by an abnormal expansion of trinucleotide CAG repeats within the huntingtin (Htt) gene. 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 differential expression analysis and H3K27ac variation in 4- and 6-week-old R6/2 mice as a model of juvenile HD. 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, a starting point for early onset indicators of the progression of this disease.
Vidal Ren¨| L.、Arancibia-Opazo Sandra、Cisternas-Olmedo Marisol、Contreras-Riquelme J. Sebasti¨￠n、S¨￠ez Mauricio A.、Martin Alberto J. M.、S¨￠nchez Mario
Centro de Biolog¨aa Integrativa, Facultad de Ciencias, Universidad Mayor||Biomedical Neuroscience Institute, University of Chile||Center for Geroscience, Brain Health, and Metabolism||Escuela de Biotecnolog¨aa, Facultad de Ciencias, Universidad MayorChromatin, Epigenetic, and Neuroscience Laboratory, Centro de Gen¨?mica y Bioinform¨￠tica, Facultad de Ciencias, Ingenier¨aa y Tecnolog¨aa, Universidad Mayor||Programa de Doctorado en Gen¨?mica Integrativa, Vicerrector¨aa de Investigaci¨?n, Universidad Mayor||Laboratorio de Redes Biol¨?gicas, Centro Cient¨afico y Tecnol¨?gico de Excelencia Ciencia & Vida, Fundaci¨?n Ciencia & Vida, Escuela de Ingenier¨aa, Facultad de Ingenier¨aa, Arquitectura y Dise?o, Universidad San Sebasti¨￠nCentro de Biolog¨aa Integrativa, Facultad de Ciencias, Universidad MayorPlant Genome Regulation Lab, Centro de Biotecnolog¨aa Vegetal, Facultad de Ciencias de la Vida, Universidad Andr¨|s BelloChromatin, Epigenetic, and Neuroscience Laboratory, Centro de Gen¨?mica y Bioinform¨￠tica, Facultad de Ciencias, Ingenier¨aa y Tecnolog¨aa, Universidad Mayor||Centro de Oncolog¨aa de precisi¨?n, Facultad de Medicina Universidad MayorLaboratorio de Redes Biol¨?gicas, Centro Cient¨afico y Tecnol¨?gico de Excelencia Ciencia & Vida, Fundaci¨?n Ciencia & Vida, Escuela de Ingenier¨aa, Facultad de Ingenier¨aa, Arquitectura y Dise?o, Universidad San Sebasti¨￠nChromatin, Epigenetic, and Neuroscience Laboratory, Centro de Gen¨?mica y Bioinform¨￠tica, Facultad de Ciencias, Ingenier¨aa y Tecnolog¨aa, Universidad Mayor
神经病学、精神病学基础医学分子生物学
Huntington’s diseaseHistone acetylationpolyQ diseasescAMP response element-binding protein
Vidal Ren¨| L.,Arancibia-Opazo Sandra,Cisternas-Olmedo Marisol,Contreras-Riquelme J. Sebasti¨￠n,S¨￠ez Mauricio A.,Martin Alberto J. M.,S¨￠nchez Mario.Transcriptional and Histone acetylation changes associated with CRE elements expose key factors governing the regulatory circuit in early stage of Huntington’s disease models[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2023.01.19.524732.点此复制
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