RT Journal Article
T1 Early alteration of epigenetic-related transcription in Huntington's disease mouse models.
A1 Hervas-Corpion, Irati
A1 Guiretti, Deisy
A1 Alcaraz-Iborra, Manuel
A1 Olivares, Roman
A1 Campos-Caro, Antonio
A1 Barco, Angel
A1 Valor, Luis M
K1 Gene expression regulation
K1 Hippocampus
K1 Huntington disease
K1 Neurons
K1 Transcriptome
AB Transcriptional dysregulation in Huntington's disease (HD) affects the expression of genes involved in survival and neuronal functions throughout the progression of the pathology. In recent years, extensive research has focused on epigenetic and chromatin-modifying factors as a causative explanation for such dysregulation, offering attractive targets for pharmacological therapies. In this work, we extensively examined the gene expression profiles in the cortex, striatum, hippocampus and cerebellum of juvenile R6/1 and N171-82Q mice, models of rapidly progressive HD, to retrieve the early transcriptional signatures associated with this pathology. These profiles were largely consistent across HD datasets, contained tissular and neuronal-specific genes and showed significant correspondence with the transcriptional changes in mouse strains deficient for epigenetic regulatory genes. The most prominent cases were the conditional knockout of the lysine acetyltransferase CBP in post-mitotic forebrain neurons, the double knockout of the histone methyltransferases Ezh1 and Ezh2, components of the polycomb repressor complex 2 (PRC2), and the conditional mutants of the histone methyltransferases G9a (Ehmt2) and GLP (Ehmt1). Based on these observations, we propose that the neuronal epigenetic status is compromised in the prodromal stages of HD, leading to an altered transcriptional programme that is prominently involved in neuronal identity.
PB Nature Publishing Group
YR 2018
FD 2018-06-18
LK http://hdl.handle.net/10668/12668
UL http://hdl.handle.net/10668/12668
LA en
NO Hervás-Corpión I, Guiretti D, Alcaraz-Iborra M, Olivares R, Campos-Caro A, Barco Á, et al. Early alteration of epigenetic-related transcription in Huntington's disease mouse models. Sci Rep. 2018 Jul 2;8(1):9925
DS RISalud
RD Apr 5, 2025