TAF6δ orchestrates an apoptotic transcriptome profile and interacts functionally with p53

Here 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.Together our data define a TAF6δ-driven apoptotic gene expression program and show crosstalk between the p53 and TAF6δ pathways.Apoptosis is an active program of cell death that is required for normal development and tissue homeostasis in metazoans [1]. The deregulation of apoptotic pathways underlies many human diseases [2]. Consequently, 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 a multiprotein complex containing the TATA-binding protein (TBP) and up to 14 evolutionarily conserved TBP-associated factors (TAFs) [6,7]. TFIID is the primary core promoter recognition complex for RNA polymerase II (pol II) and thus plays a key role in the regulation of transcription of protein-coding genes [8]. The major TAF6α isoform is ubiquitously expressed [9] whereas strong expression of the TAF6δ isoform has only been detected in apoptotic conditions (e.g. HL-60 cells undergoing retinoic acid dependent death) [4]. The use of modified antisense RNA oligonucleotides, also termed splice-switching oligonucleotides (SSO), to experimentally direct the expression of endogeno