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

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

PROVIDER: PRJNA635627 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11866747.fastq.gz	Fastqsanger.gz
	SRR11866748.fastq.gz	Fastqsanger.gz
	SRR11866749.fastq.gz	Fastqsanger.gz
	SRR11866750.fastq.gz	Fastqsanger.gz
	SRR11866751.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]

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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 [ATAC-seq]

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

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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

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

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

| PRJNA635633 | 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

TAF4 promotes pre-initiation complex formation and HNF4A occupancy of regulatory elements required to activation post-natal gene expression programme in hepatocytes (RNA-seq)

Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. RNA profiles in wild-type and Taf4-/- livers by deep sequencing

2014-09-25 | E-GEOD-57712 | biostudies-arrayexpress

TAF4 promotes pre-initiation complex formation and HNF4A occupancy of regulatory elements required to activation post-natal gene expression programme in hepatocytes (ChIP-seq)

Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Examination of PIC, H3k4me3, Ctcf and Hnf4a occupancy in wild-type and Taf4-/- livers by deep sequencing

2014-09-25 | E-GEOD-57807 | biostudies-arrayexpress

TAF4 promotes pre-initiation complex formation and HNF4A occupancy of regulatory elements required to activation post-natal gene expression programme in hepatocytes (ChIP-seq)

2014-09-25 | GSE57807 | GEO