TAF6δ Controls Apoptosis and Gene Expression in the Absence of p53

Wilhelm, Emmanuelle; Pellay, François-Xavier; Benecke, Arndt; Bell, Brendan

doi:10.1371/journal.pone.0002721

Cited by 13 publications

(57 citation statements)

References 65 publications

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“…Our previous work demonstrated that TAF6δ induces apoptosis independently of p53 [5]. Interestingly, the current transcriptome data show that TAF6δ induces the expression of several p53 target genes (Figure 2A and Additional File 3).…”

Section: Resultsmentioning

confidence: 67%

TAF6δ orchestrates an apoptotic transcriptome profile and interacts functionally with p53

et al. 2010

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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.

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Section: Resultsmentioning

confidence: 67%

TAF6δ orchestrates an apoptotic transcriptome profile and interacts functionally with p53

et al. 2010

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“…Particularly illustrative of the regulatory power of alternative TAFs is that overexpression of TAF6, or induction of endogenous TAF6 expression, in HeLa cells induces apoptotic cell death and the transcription of pro-apoptotic genes in the absence of an apoptotic signal. Surprisingly, the pro-apoptotic transcription factor p53 (TP53) is not required for TAF6-dependent transcription or apoptosis (Wilhelm et al, 2008). Similarly, overexpression of TAF4b in non-granulosa cells, such as mouse NIH/3T3 fibroblasts, results in the expression of genes that are TAF4b dependent in ovaries and granulosa cells and that are not normally expressed in non-granulosa cells (Geles et al, 2006).…”

Section: Master Transcriptional Control By Tafsmentioning

confidence: 99%

Promoting developmental transcription

Ohler

Wassarman

2010

Development

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Animal growth and development depend on the precise control of gene expression at the level of transcription. A central role in the regulation of developmental transcription is attributed to transcription factors that bind DNA enhancer elements, which are often located far from gene transcription start sites. Here, we review recent studies that have uncovered significant regulatory functions in developmental transcription for the TFIID basal transcription factors and for the DNA core promoter elements that are located close to transcription start sites.

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“…3A), and because modified antisense RNA oligonucleotides that anneal to it can shift the splicing from the major to the pro-apoptotic δ form in living cells [3]. The ESEfinder algorithm [34] was employed and detected a potential SF2 binding site in exon 2a (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Taken together these findings suggest that the major anti-apoptotic TAF6α splice variant possesses oncogenic potential. In stark contrast, the minor TAF6δ splice variant has pro-apoptotic activity evoking a potential tumor suppressor activity [1], [2], [3]. It is conceivable that anti-apoptotic TAF6α expression can be decoupled from pro-apoptotic TAF6δ in certain tumor types.…”

Section: Discussionmentioning

confidence: 99%

Alternative Splicing of TAF6: Downstream Transcriptome Impacts and Upstream RNA Splice Control Elements

et al. 2014

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The TAF6δ pathway of apoptosis can dictate life versus death decisions independently of the status of p53 tumor suppressor. TAF6δ is an inducible pro-apoptotic subunit of the general RNA polymerase II (Pol II) transcription factor TFIID. Alternative splice site choice of TAF6δ has been shown to be a pivotal event in triggering death via the TAF6δ pathway, yet nothing is currently known about the mechanisms that promote TAF6δ splicing. Furthermore the transcriptome impact of the gain of function of TAF6δ versus the loss of function of the major TAF6α splice form remains undefined. Here we employ comparative microarray analysis to show that TAF6δ drives a transcriptome profile distinct from that resulting from depletion of TAF6α. To define the cis-acting RNA elements responsible for TAF6δ alternative splicing we performed a mutational analysis of a TAF6 minigene system. The data point to several new RNA elements that can modulate TAF6δ and also reveal a role for RNA secondary structure in the selection of TAF6δ.

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TAF6δ Controls Apoptosis and Gene Expression in the Absence of p53

Cited by 13 publications

References 65 publications

TAF6δ orchestrates an apoptotic transcriptome profile and interacts functionally with p53

TAF6δ orchestrates an apoptotic transcriptome profile and interacts functionally with p53

Promoting developmental transcription

Alternative Splicing of TAF6: Downstream Transcriptome Impacts and Upstream RNA Splice Control Elements

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