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oai:riuma.uma.es:10630/334012026-02-03T11:05:41Zcom_10630_2254col_10630_37953

KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain. Lipinski, Michal Muñoz-Viana, Rafael del Blanco, Beatriz Márquez-Galera, Ángel Medrano-Relinque, Juan Caramés-Tejedor, José María Szczepankiewicz, Andrzej A. Fernández-Albert, Jordi Navarrón, Carmen M. Olivares, Román Wilczyński, Grzegorz M. Canals-Gamoneda, Santiago López-Atalaya, José P. Barco, Ángel Ratones - Cerebro Proteínas Neurociencias The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions. 2024-09-26T09:24:45Z 2024-09-26T09:24:45Z 2024-09-26T09:24:45Z 2020-05-22 journal article Lipinski, M., Muñoz-Viana, R., del Blanco, B. et al. KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain. Nat Commun 11, 2588 (2020). https://hdl.handle.net/10630/33401 10.1038/s41467-020-16246-0 eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 Internacional Nature Communications, Nature Publishng Group