التفاصيل البيبلوغرافية
| العنوان: |
KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain. |
| المؤلفون: |
Lipinski, Michal, Muñoz-Viana, Rafael, del Blanco, Beatriz, Marquez-Galera, Angel, Medrano-Relinque, Juan, Caramés, José M., Szczepankiewicz, Andrzej A., Fernandez-Albert, Jordi, Navarrón, Carmen M., Olivares, Roman, Wilczyński, Grzegorz M., Canals, Santiago, Lopez-Atalaya, Jose P., Barco, Angel |
| المصدر: |
Nature Communications; 5/22/2020, Vol. 11 Issue 1, p1-18, 18p |
| مصطلحات موضوعية: |
ACETYLATION, HISTONE acetylation, GENES, TRANSCRIPTION factors, GENE expression, DENDRITIC spines |
| مستخلص: |
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. Neuronal identity maintenance is highly regulated. Here, the authors showed that CBP and p300 safeguard neuronal identity through histone acetylation at promoters and enhancers of neuronal specific genes. The loss of both CBP and p300 impairs gene expression, circuit activity, and behavior in mice. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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