title: Specific promoter deacetylation of histone H3 is conserved across mouse models of Huntington's disease in the absence of bulk changes.
abstract: Defective epigenetic regulation has been postulated as a possible cause for the extensive and premature transcriptional dysregulation observed in experimental models of Huntington's disease (HD). In this study, we extended our observations in the N171-82Q mouse strain relating to the limited impact of polyQ pathology on the global histone acetylation to other animal and cellular models of HD, namely the R6/1 and YAC128 strains, striatal-electroporated mice, primary neuronal cultures and stably transfected PC12 cells. In the absence of bulk chromatin changes, we nonetheless documented histone deacetylation events at the transcription start sites (TSS) of genes relevant to neuronal functions (e.g., Rin1, Plk5, Igfbp5, Eomes, and Fos). In some instances, these local deficits were associated with an increased susceptibility to transcriptional dysregulation (e.g., Camk1g and Rasl11b) and the defective trimethylation of histone H3 at lysine 4 (H3K4me3), another covalent modification of histone tails that is related to active transcription and is also altered in HD. Overall, this study provides further insight into the nature and extent of epigenetic dysregulation in HD pathology.
authors: Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Av. Santiago Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain.
authors: Deisy
authors: D
authors: Guiretti
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Av. de la Universidad s/n, 03202 Elche, Spain.
authors: Ana
authors: A
authors: Sempere
authors: Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Av. Santiago Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain.
authors: Jose P
authors: JP
authors: Lopez-Atalaya
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Av. de la Universidad s/n, 03202 Elche, Spain.
authors: Antonio
authors: A
authors: Ferrer-Montiel
authors: Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Av. Santiago Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain. Electronic address: abarco@umh.es.
authors: Angel
authors: A
authors: Barco
authors: Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Av. Santiago Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain; Unidad de Investigación, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 Cádiz, Spain. Electronic address: luism.valor.exts@juntadeandalucia.es.
authors: Luis M
authors: LM
authors: Valor
mesh_terms: D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D051381:Rats
chemical_list: D002843:Chromatin; D006657:Histones
keywords: Epigenetics; Histone acetylation; Histone methylation; Huntington's disease; Polyglutamine; Transcriptional dysregulation