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Loss of TAF8 causes TFIID dysfunction and p53-mediated apoptotic neuronal cell death.


ABSTRACT: Mutations in genes encoding general transcription factors cause neurological disorders. Despite clinical prominence, the consequences of defects in the basal transcription machinery during brain development are unclear. We found that loss of the TATA-box binding protein-associated factor TAF8, a component of the general transcription factor TFIID, in the developing central nervous system affected the expression of many, but notably not all genes. Taf8 deletion caused apoptosis, unexpectedly restricted to forebrain regions. Nuclear levels of the transcription factor p53 were elevated in the absence of TAF8, as were the mRNAs of the pro-apoptotic p53 target genes Noxa, Puma and Bax. The cell death in Taf8 forebrain regions was completely rescued by additional loss of p53, but Taf8 and p53 br

SUBMITTER: El-Saafin F 

PROVIDER: S-EPMC9091217 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature