Transcriptional and Histone Acetylation Changes Associated with CRE Elements Expose Key Factors Governing the Regulatory Circuit in the Early Stage of Huntington’s Disease Models

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dc.contributor.authorArancibia-Opazo, Sandra
dc.contributor.authorContreras-Riquelme, J. Sebastián
dc.contributor.authorSánchez, Mario
dc.contributor.authorCisternas-Olmedo, Marisol
dc.contributor.authorVidal, René L.
dc.contributor.authorMartin, Alberto J. M.
dc.contributor.authorSáez, Mauricio A.
dc.date.accessioned2023-08-16T19:42:19Z
dc.date.available2023-08-16T19:42:19Z
dc.date.issued2023-06
dc.descriptionIndexación:Scopuses
dc.description.abstractHuntington’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 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. © 2023 by the authors.es
dc.description.urihttps://www.mdpi.com/1422-0067/24/13/10848
dc.identifier.doi10.3390/ijms241310848
dc.identifier.issn1661- 6596
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/52559
dc.language.isoenes
dc.publisherMDPIes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectcAMP response element-binding proteines
dc.subjectGene regulatory networkses
dc.subjectHistone acetylation;histone acetylationes
dc.subjectHuntington’s diseasees
dc.subjectPolyQ diseaseses
dc.titleTranscriptional and Histone Acetylation Changes Associated with CRE Elements Expose Key Factors Governing the Regulatory Circuit in the Early Stage of Huntington’s Disease Modelses
dc.typeArtículoes
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