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Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation

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

ORGANISM(S): Mus musculus

PROVIDER: GSE145612 | GEO | 2020/11/25

REPOSITORIES: GEO

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GATA2 regulates mast cell identity and responsiveness to antigenic stimulation by promoting chromatin remodeling at super-enhancers.

Project description:Mast cells are critical effectors of allergic inflammation and protection against parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors. However, it is unclear whether these lineage-determining factors regulate chromatin accessibility at mast cell enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation. We find that the number and densities of GATA2- but not MITF-bound sites at the super-enhancers are several folds higher than that at the typical enhancers. Our studies reveal that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation by binding to super-enhancer regions with dense GATA2 binding sites available at key mast cell genes.

| S-EPMC7820599 | biostudies-literature

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [RNA-seq]

Project description:Mast cells are critical effectors in causing allergic inflammation and in protecting against certain parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors (LDTFs). However, it is unclear whether these LDTFs play a role in regulating chromatin accessibility at the enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both the typical and super-enhancers at the genes that respond to antigenic stimulation. We found that the number and densities of GATA2, but not MITF, -bound sites at the super-enhancers were several folds higher than that at the typical enhancers. Our study reveals that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation simply by binding to a larger number of GATA2 binding sites available at the super-enhancers of the key mast cell genes.

2020-11-25 | GSE145611 | GEO

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [ChIP-seq]

2020-11-25 | GSE145544 | GEO

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [ATAC-seq]

2020-11-25 | GSE145542 | GEO

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation

Project description:Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation

| PRJNA607740 | ENA

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [ATAC-seq]

Project description:Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [ATAC-seq]

| PRJNA607533 | ENA

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [ChIP-seq]

| PRJNA607532 | ENA

Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [RNA-seq]

| PRJNA607738 | ENA

Master transcription factors and mediator establish super-enhancers at key cell identity genes.

Project description:Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity.

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Super-enhancers in the control of cell identity and disease.

Project description:Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity. Improved understanding of the roles that super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. We produce a catalog of super-enhancers in a broad range of human cell types and find that super-enhancers associate with genes that control and define the biology of these cells. Interestingly, disease-associated variation is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes important in tumor pathogenesis. Thus, super-enhancers play key roles in human cell identity in health and in disease.

| S-EPMC3841062 | biostudies-literature

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