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The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes

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

ORGANISM(S): Mus musculus

PROVIDER: GSE171410 | GEO | 2022/03/30

REPOSITORIES: GEO

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The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [RNA-seq]

Project description:Differentiation of progenitor cells into mature cell types is commonly associated with the expression of lineage-determining transcription factors (LD-TFs) specific to that lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. LD-TFs, including T-bet and GATA3, are frequently co-expressed, both in vitro and in vivo. How co-expression of two mutually antagonistic LD-TFs affects their function and lineage determination is not known. By expressing T-bet and GATA3 separately or together, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. T-bet interacts with the GATA3 DNA binding domain, changing its DNA sequence binding preference. This mechanism allows T-bet to dominate and drive the TH1 gene expression program in the presence of the GATA3. We propose that redistribution of one LD-TF by another may be a common mechanism that could explain how specific cell fate choices can be made even in the presence of other TFs driving alternative differentiation pathways.

2022-03-30 | GSE171409 | GEO

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq]

2022-03-30 | GSE171408 | GEO

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ATAC-seq]

2022-03-30 | GSE171407 | GEO

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq series 2]

2022-03-30 | GSE196508 | GEO

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes

Project description:The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes

| PRJNA719401 | ENA

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ATAC-seq]

Project description:The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ATAC-seq]

| PRJNA719405 | ENA

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq]

Project description:The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq]

| PRJNA719406 | ENA

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [RNA-seq]

Project description:The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [RNA-seq]

| PRJNA719407 | ENA

The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq series 2]

Project description:The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq series 2]

| PRJNA805234 | ENA

T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements.

Project description:T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little is known about the interplay between these factors outside of the murine Ifng and Il4/Il5/Il13 loci. Here we show that T-bet and GATA3 bind to multiple distal sites at immune regulatory genes in human effector T cells. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with a requirement for T-bet and GATA3. Furthermore, we demonstrate that both factors bind distal sites at Tbx21 and that T-bet directly activates its own expression. We also show that in Th1 cells, GATA3 is distributed away from Th2 genes, instead occupying T-bet binding sites at Th1 genes, and that T-bet is sufficient to induce GATA3 binding at these sites. We propose these aspects of T-bet and GATA3 function are important for Th1/Th2 differentiation and for understanding transcription factor interactions in other T cell lineage decisions.

| S-EPMC3535338 | biostudies-literature

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