KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain.
Michal LipinskiRafael Muñoz-VianaBeatriz Del BlancoAngel Marquez-GaleraJuan Medrano-RelinqueJosé M CaramésAndrzej Antoni SzczepankiewiczJordi Fernandez-AlbertCarmen M NavarrónRoman OlivaresGrzegorz M WilczyńskiSantiago CanalsJose P Lopez-AtalayaÁngel BarcoPublished in: Nature communications (2020)
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.
Keyphrases
- transcription factor
- cerebral ischemia
- spinal cord
- genome wide identification
- gene expression
- dna methylation
- histone deacetylase
- binding protein
- subarachnoid hemorrhage
- spinal cord injury
- endothelial cells
- brain injury
- blood brain barrier
- anti inflammatory
- cell cycle
- amino acid
- heat shock
- childhood cancer
- high fat diet induced
- heat shock protein
- temporal lobe epilepsy