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https://hdl.handle.net/2440/135444
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Type: | Journal article |
Title: | Loss of TAF8 causes TFIID dysfunction and p53-mediated apoptotic neuronal cell death |
Author: | El-Saafin, F. Bergamasco, M.I. Chen, Y. May, R.E. Esakky, P. Hediyeh-zadeh, S. Dixon, M. Wilcox, S. Davis, M.J. Strasser, A. Smyth, G.K. Thomas, T. Voss, A.K. |
Citation: | Cell Death and Differentiation, 2022; 29(5):1013-1027 |
Publisher: | Springer Science and Business Media LLC |
Issue Date: | 2022 |
ISSN: | 1350-9047 1476-5403 |
Statement of Responsibility: | Farrah El-Saafin, Maria I. Bergamasco, Yunshun Chen, Rose E. May, Prabagaran Esakky, Soroor Hediyeh-zadeh, Mathew Dixon, Stephen Wilcox, Melissa J. Davis, Andreas Strasser, Gordon K. Smyth, Tim Thomas, and Anne K. Voss |
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. |
Keywords: | Animals Mice Transcription Factor TFIID Transcription Factors Cell Death Apoptosis Transcription, Genetic Tumor Suppressor Protein p53 |
Rights: | Copyright © 2022, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare |
DOI: | 10.1038/s41418-022-00982-5 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/215301 http://purl.org/au-research/grants/nhmrc/1084504 http://purl.org/au-research/grants/nhmrc/1016701 http://purl.org/au-research/grants/nhmrc/1003435 http://purl.org/au-research/grants/nhmrc/575512 http://purl.org/au-research/grants/nhmrc/1081421 http://purl.org/au-research/grants/nhmrc/1020363 http://purl.org/au-research/grants/nhmrc/1154970 http://purl.org/au-research/grants/nhmrc/1176789 http://purl.org/au-research/grants/nhmrc/1176199 |
Published version: | http://dx.doi.org/10.1038/s41418-022-00982-5 |
Appears in Collections: | Medical Sciences publications |
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