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

PROVIDER: PRJNA719401 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14136229_1.fastq.gz	Fastqsanger.gz
	SRR14136229_2.fastq.gz	Fastqsanger.gz
	SRR14136230_1.fastq.gz	Fastqsanger.gz
	SRR14136230_2.fastq.gz	Fastqsanger.gz
	SRR14136231_1.fastq.gz	Fastqsanger.gz

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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]

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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]

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

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

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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.

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

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Bcl11b- and GATA3-mediated gene regulation in Th2 cells

Project description:GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we report that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein-protein interaction, and they co-localize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5 and IL-13, is up-regulated in Bcl11b-deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3-dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated gene (from RNA-Seq), co-binding pattern (from ChIP-Seq), and Bcl11b-mediated epigenetic changes (in H3K27ac and DHSs) suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells.

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

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

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