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

El-Saafin, F; Bergamasco, MI; Chen, Y; May, RE; Esakky, P; Hediyeh-Zadeh, S; Dixon, M; Wilcox, S; Davis, MJ; Strasser, A; Smyth, GK; Thomas, T; Voss, AK

Author(s): El-Saafin, F; Bergamasco, MI; Chen, Y; May, RE; Esakky, P; Hediyeh-Zadeh, S; Dixon, M; Wilcox, S; Davis, MJ; Strasser, A; Smyth, GK; Thomas, T; Voss, AK;
Details: Publication Year 2022-05,Volume 29,Issue #5,Page 1013-1027
Journal Title: Cell Death and Differentiation
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 brains failed to initiate a neuronal expression program. Taf8 deletion caused aberrant transcription of promoter regions and splicing anomalies. We propose that TAF8 supports the directionality of transcription and co-transcriptional splicing, and that failure of these processes causes p53-induced apoptosis of neuronal cells in the developing mouse embryo.
Publisher: NPG
Keywords: Animals; Apoptosis/genetics; Cell Death; Mice; *Transcription Factor TFIID/genetics/metabolism; Transcription Factors/*metabolism; Transcription, Genetic; *Tumor Suppressor Protein p53/genetics/metabolism
Research Division(s): Bioinformatics; Advanced Technology And Biology; Blood Cells And Blood Cancer; Epigenetics And Development; Infectious Diseases And Immune Defence
PubMed ID: 35361962
Publisher's Version: https://doi.org/10.1038/s41418-022-00982-5
NHMRC Grants: NHMRC/1016701, NHMRC/1020363, NHMRC/1084504, NHMRC/1003435, NHMRC/215301, NHMRC/575512, NHMRC/1081421,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2022-07-13 03:16:51

Last Modified: 2022-07-13 03:21:10