Loss of TAF8 causes TFIID dysfunction and p53-mediated apoptotic neuronal cell death.
Cell Death Differ
; 29(5): 1013-1027, 2022 05.
Article
in En
| MEDLINE
| ID: mdl-35361962
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Tumor Suppressor Protein p53
/
Transcription Factor TFIID
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Cell Death Differ
Year:
2022
Type:
Article
Affiliation country:
Australia