RT Journal Article
T1 KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain.
A1 Lipinski, Michal
A1 Muñoz-Viana, Rafael
A1 del Blanco, Beatriz
A1 Márquez-Galera, Ángel
A1 Medrano-Relinque, Juan
A1 Caramés-Tejedor, José María
A1 Szczepankiewicz, Andrzej A.
A1 Fernández-Albert, Jordi
A1 Navarrón, Carmen M.
A1 Olivares, Román
A1 Wilczyński, Grzegorz M.
A1 Canals-Gamoneda, Santiago
A1 López-Atalaya, José P.
A1 Barco, Ángel
K1 Ratones - Cerebro
K1 Proteínas
K1 Neurociencias
AB 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.
PB Nature Communications, Nature Publishng Group
YR 2020
FD 2020-05-22
LK https://hdl.handle.net/10630/33401
UL https://hdl.handle.net/10630/33401
LA eng
NO 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).
NO The ultrastructure research was sup- ported by the Polish National Science Center Grant UMO-2014/15/N/NZ3/04468 and by the European Regional Development Fund POIG 01.01.02-00-008/08. J.P.L.-A. research is supported by Grants RYC-2015-18056 and RTI2018-102260-B-I00 from MICINN co- financed by ERDF. A.B. research is supported by Grants SAF2017-87928-R, PCIN-2015- 192-C02-01, and SEV-2017-0723 from MICINN co-financed by ERDF, PROMETEO/ 2016/026 from the Generalitat Valenciana, and RGP0039/2017 from the Human Fron- tiers Science Program Organization (HFSPO). The Instituto de Neurociencias is a “Centre of Excellence Severo Ochoa”.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026