Abstract
BackgroundTFIID is a multiprotein complex that plays a pivotal role in the regulation of RNA polymerase II (Pol II) transcription owing to its core promoter recognition and co-activator functions. TAF6 is a core TFIID subunit whose splice variants include the major TAF6α isoform that is ubiquitously expressed, and the inducible TAF6δ. In contrast to TAF6α, TAF6δ is a pro-apoptotic isoform with a 10 amino acid deletion in its histone fold domain that abolishes its interaction with TAF9. TAF6δ expression can dictate life versus death decisions of human cells.ResultsHere we define the impact of endogenous TAF6δ expression on the global transcriptome landscape. TAF6δ was found to orchestrate a transcription profile that included statistically significant enrichment of genes of apoptotic function. Interestingly, gene expression patterns controlled by TAF6δ share similarities with, but are not equivalent to, those reported to change following TAF9 and/or TAF9b depletion. Finally, because TAF6δ regulates certain p53 target genes, we tested and demonstrated a physical and functional interaction between TAF6δ and p53.ConclusionTogether our data define a TAF6δ-driven apoptotic gene expression program and show crosstalk between the p53 and TAF6δ pathways.
Highlights
TFIID is a multiprotein complex that plays a pivotal role in the regulation of RNA polymerase II (Pol II) transcription owing to its core promoter recognition and co-activator functions
The TAF6δ orchestrates a pro-apoptotic gene expression program To establish the impact of TAF6δ on global gene expression patterns, the expression of the endogenous
We note that to achieve the statistically significant overrepresentation of gene ontology pathways reported here it was necessary to employ optimized splice-switching oligonucleotides (SSO) sequences designed to more efficiently induce TAF6δ expression than those employed in a previous study [5]
Summary
TFIID is a multiprotein complex that plays a pivotal role in the regulation of RNA polymerase II (Pol II) transcription owing to its core promoter recognition and co-activator functions. TAF6 is a core TFIID subunit whose splice variants include the major TAF6a isoform that is ubiquitously expressed, and the inducible TAF6δ. Apoptotic pathways represent potential targets for therapeutic control of cell death for diseases including neurodegenerative disorders, autoimmune diseases and cancer [3]. Our previous studies have uncovered the existence of an apoptotic pathway termed the TAF6δ pathway that controls cell death [4,5]. TAF6δ is an inducible splice variant of the TFIID subunit TAF6 (previously termed hTAFII70 or hTAFII80). TFIID is the primary core promoter recognition complex for RNA polymerase II (pol II) and plays a key role in the
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