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

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dc.contributor.authorEl-Saafin, F.
dc.contributor.authorBergamasco, M.I.
dc.contributor.authorChen, Y.
dc.contributor.authorMay, R.E.
dc.contributor.authorEsakky, P.
dc.contributor.authorHediyeh-zadeh, S.
dc.contributor.authorDixon, M.
dc.contributor.authorWilcox, S.
dc.contributor.authorDavis, M.J.
dc.contributor.authorStrasser, A.
dc.contributor.authorSmyth, G.K.
dc.contributor.authorThomas, T.
dc.contributor.authorVoss, A.K.
dc.date.issued2022
dc.description.abstractMutations 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.
dc.description.statementofresponsibilityFarrah 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
dc.identifier.citationCell Death and Differentiation, 2022; 29(5):1013-1027
dc.identifier.doi10.1038/s41418-022-00982-5
dc.identifier.issn1350-9047
dc.identifier.issn1476-5403
dc.identifier.orcidDavis, M.J. [0000-0003-4864-7033]
dc.identifier.urihttps://hdl.handle.net/2440/135444
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/215301
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1084504
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016701
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1003435
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/575512
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1081421
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1020363
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1154970
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1176789
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1176199
dc.rightsCopyright © 2022, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare
dc.source.urihttps://doi.org/10.1038/s41418-022-00982-5
dc.subjectAnimals
dc.subjectMice
dc.subjectTranscription Factor TFIID
dc.subjectTranscription Factors
dc.subjectCell Death
dc.subjectApoptosis
dc.subjectTranscription, Genetic
dc.subjectTumor Suppressor Protein p53
dc.subject.meshAnimals
dc.subject.meshMice
dc.subject.meshTranscription Factor TFIID
dc.subject.meshTranscription Factors
dc.subject.meshCell Death
dc.subject.meshApoptosis
dc.subject.meshTranscription, Genetic
dc.subject.meshTumor Suppressor Protein p53
dc.titleLoss of TAF8 causes TFIID dysfunction and p53-mediated apoptotic neuronal cell death
dc.typeJournal article
pubs.publication-statusPublished

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