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The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [single-cell RNA-seq]

ABSTRACT: The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [single-cell RNA-seq]

PROVIDER: PRJNA635633 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11866759_1.fastq.gz	Fastqsanger.gz
	SRR11866759_2.fastq.gz	Fastqsanger.gz
	SRR11866760_1.fastq.gz	Fastqsanger.gz
	SRR11866760_2.fastq.gz	Fastqsanger.gz
	SRR11866761_1.fastq.gz	Fastqsanger.gz

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The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [RNA-seq]

Project description:We selectively inactivated the Taf4 subunit of general transcription factor TFIID in adult murine pancreatic beta cells (BCs). Taf4 inactivation rapidly diminishes expression of critical genes involved in BC function leading to increased glycaemia, lowered blood insulin levels, defective glucose-stimulated insulin secretion and in the longer term reduced BC mass through apoptosis of a subpopulation of BCs. Nevertheless, glycaemia and blood insulin levels are stabilised after 11 weeks with mutant animals showing long term survival. Bulk RNA-seq and ATAC-seq and single cell RNA-seq on isolated Langerhans islets show that Taf4 loss leads to major remodelling of chromatin accessibility and gene expression not only in targeted BCs, but also alpha and delta cells. One week after Taf4-loss cells with mixed BC, alpha and/or delta cell identities were observed as well as a population trans-differentiating into alpha cells. Trans-differentiation was associated with the concerted action of the Mafb, Mafg, Bptf and Foxp1 transcription factors. Taf4 is therefore essential for BC function and identity and we identify a novel set of factors associated with BC trans-differentiation.

2021-06-01 | GSE151364 | GEO

The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [ATAC-seq]

2021-06-01 | GSE151363 | GEO

The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [single-cell RNA-seq]

2021-06-01 | GSE151365 | GEO

The TFIID subunit TAF4 is required for pancreatic beta cell function and identity

Project description:The TFIID subunit TAF4 is required for pancreatic beta cell function and identity

| PRJNA635627 | ENA

The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [ATAC-seq]

Project description:The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [ATAC-seq]

| PRJNA635632 | ENA

The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [RNA-seq]

Project description:The TFIID subunit TAF4 is required for pancreatic beta cell function and identity [RNA-seq]

| PRJNA635634 | ENA

A TAF4 coactivator function for E proteins that involves enhanced TFIID binding

Project description:The multisubunit TFIID plays a direct role in transcription initiation by binding to core promoter elements and directing preinitiation complex assembly. Although TFIID may also function as a coactivator through direct interactions with promoter-bound activators, mechanistic aspects of this poorly defined function remain unclear. Here biochemical studies show a direct TFIID-E protein interaction that (i) is mediated through interaction of a novel E protein activation domain (AD3) with the TAF homology (TAFH) domain of TAF4, (ii) is critical for activation of a natural target gene by an E protein and (iii) mechanistically, acts by enhancing TFIID binding to the core promoter. Complementary assays establish a gene-specific role for the TAFH domain in TFIID recruitment and gene activation in vivo. These results firmly establish TAF4 as a bona fide E protein coactivator, as well as a mechanism involving facilitated TFIID binding through direct interaction with an E protein activation domain. Genome-wide profiling of mRNA levels in MEF lines with Taf4 loxp/- (ctrl), Taf4 -/- (ko), Taf4 -/- Tg:hTAF4 wt, and Taf4 -/- Tg: hTAF4 ? (TAFH-deleted).

2013-06-06 | E-GEOD-46807 | biostudies-arrayexpress

A TAF4 coactivator function for E proteins that involves enhanced TFIID binding

2013-06-06 | GSE46807 | GEO

TFIID subunit TAF4 is essential at mid-gestation of murine embryogenesis and for embryonic stem cell differentiation

Project description:TFIID subunit TAF4 is essential at mid-gestation of murine embryogenesis and for embryonic stem cell differentiation

| PRJNA289445 | ENA

Gene expression changes associated with 3D growth of TAF4 knock out fibroblasts

Project description:Collagen 6A3 (Col6a3), a component of extracellular matrix, is often up-regulated in tumours and is believed to play a pro-oncogenic role. However the mechanisms of its tumorigenic activity are poorly understood. We show here that Col6a3 is highly expressed in densely growing mouse embryonic fibroblasts (MEFs). In MEFs where the TAF4 subunit of general transcription factor IID (TFIID) has been inactivated, elevated Col6a3 expression prevents contact inhibition promoting their 3 dimensional growth as foci and fibrospheres. Analyses of gene expression in densely growing Taf4-/- MEFs revealed repression of the Hippo pathway and activation of Wnt signalling. The Hippo activator Kibra/Wwc1 is repressed under dense conditions in Taf4-/- MEFs, leading to nuclear accumulation of the proliferation factor YAP1 in the cells forming 3D foci. At the same time, Wnt9a is activated and the Sfrp2 antagonist of Wnt signalling is repressed. Surprisingly, treatment of Taf4-/- MEFs with all-trans retinoic acid (ATRA) restores contact inhibition suppressing 3D growth. ATRA represses Col6a3 expression independently of TAF4 expression and Col6a3 silencing is sufficient to restore contact inhibition in Taf4-/- MEFs and to suppress 3D growth by reactivating Kibra expression to induce Hippo signalling and by inducing Sfrp2 expression to antagonize Wnt signalling. All together, these results reveal a critical role for Col6a3 in regulating both Hippo and Wnt signalling to promote 3D growth, and show that the TFIID subunit TAF4 is essential to restrain the growth promoting properties of Col6a3. Our data provide new insight into the role of extra cellular matrix components in regulating cell growth. 6 samples corresponding to non-confluent cells, confluent cells and cells growing as fibrospheres were analyzed. Each growing condition was done in duplicate.

2014-03-06 | E-GEOD-53098 | biostudies-arrayexpress

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