Study of the relationship between H3K27 acetylation levels and transcriptional changes associate with CRE promoters in Huntington Disease model

Arancibia-Opazo, Sandra; Martin, Alberto J. M.; Sáez-Venegas, Mauricio

Abstract

Study of the relationship between H3K27 acetylation levels and transcriptional changes associate with CRE promoters in Huntington Disease models Sandra Arancibia-Opazo123*, Alberto J.M. Martin3, Mauricio Sáez-Venegas21 Programa de Doctorado en Genómica Integrativa, Universidad Mayor, Chile 2 CENLAB. Centro de genómica y bioinformática, Universidad Mayor, Chile 3 Network Biology Laboratory. Centro de genómica y bioinformática, Universidad Mayor, Chile *[email protected] Huntington's disease (HD) is a neurodegenerative, autosomal dominant and hereditary disorder, with symptoms manifested between 30 - 50 years old [1] [2]. However, 5% of cases affect people under 20 years old [2]. This disease is caused by an abnormal expansion of the CAG segment of polyglutamines (polyQ) in the N-terminal region of the IT15 gene that codes for the huntingtin protein [1] [2] [3]. Also, HD is characterized by generate aggregates in nuclear inclusions caused by the mutation of the huntingtin protein together with the death of striated body neurons and the cerebral cortex [4] [5]. Epigenetic deregulation and transcriptional deregulation have emerged as common pathological mechanisms in many neurological disorders, especially HD [6] [7]. In animal’s models with HD, the mutant huntingtin (mHTT) protein has been sequestered as a nuclear aggregate to the CREB binding protein (CBP), causing a loss of function, impaired neuronal histone acetylation, cellular toxicity and transcriptional deregulation [4] [5]. Given this, the cAMP response element binding protein (CREB) that is transcriptionally activated by CBP, could see the transcriptional activity of CREB diminished and therefore decrease the activity of the CRE promoter [8] [9]. In this work, using transcriptomic information of the murine R6 /1 model, obtained from the NCBI-SRA database [10], a bioinformatics analysis was performed to identify transcriptional changes that occur in healthy condition versus HD, related to changes in the levels of acetylation of H3K27 and that have some involvement with the CRE promoter. Subsequently, through a differential network analysis, changes in transcriptional pathways that are altered will be sought given the changes in acetylation levels, produced by the decrease in CBP levels

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Fecha de publicación: 2019
Año de Inicio/Término: 28 al 30 de Octubre 2019