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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE151366 | GEO | 2021/06/01

REPOSITORIES: GEO

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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

Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4.

Project description:Regulation of gene expression involves a complex and dynamic dialogue between transcription factors, chromatin remodelling and modification complexes and the basal transcription machinery. To address the function of the Taf4 subunit of general transcription factor TFIID in the regulation of insulin signalling, it was inactivated in adult murine pancreatic beta cells. Taf4 inactivation impacted the expression of critical genes involved in beta-cell function leading to increased glycaemia, lowered plasma insulin levels and defective glucose-stimulated insulin secretion. One week after Taf4-loss, single-cell RNA-seq revealed cells with mixed beta cell, alpha and/or delta cell identities as well as a beta cell population trans-differentiating into alpha-like cells. Computational analysis of single-cell RNA-seq defines how known critical beta cell and alpha cell determinants may act in combination with additional transcription factors and the NuRF chromatin remodelling complex to promote beta cell trans-differentiation.

| S-EPMC8361202 | biostudies-literature

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

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

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-03-20 | GSE70726 | GEO

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 (1) is mediated through interaction of a novel E-protein activation domain (activation domain 3 [AD3]) with the TAF homology (TAFH) domain of TAF4, (2) is critical for activation of a natural target gene by an E protein, and (3) 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 activation of a large subset of genes 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.

| S-EPMC3731548 | biostudies-literature

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