The murine 900 kb downsteam region from Gata3 interacts to the transciption start site and three enhancers in Th2 cells.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE241990 | GEO | 2024/07/17
REPOSITORIES: GEO
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Project description:Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling and increased expression of a set of Th2-specific genes including those encoding Th2 cytokines. IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression. However, it remains unclear whether the expression of other Th2-specific genes is induced directly by GATA3. A genome-wide unbiased ChIP-seq analysis revealed that GATA3 bound to 1,279 genes selectively in Th2 cells, and 101 genes in both Th1 and Th2 cells. Simultaneously, we identified 26 highly Th2-specific STAT6-dependent inducible genes by a DNA microarray analysis-based three-step selection processes, and among them 17 genes showed GATA3 binding. We assessed dependency on GATA3 for the transcription of these 26 Th2-specific genes, and 10 genes showed increased transcription in a GATA3-dependent manner while 16 genes showed no significant responses. The transcription of the 16 GATA3-nonresponding genes was clearly increased by the introduction of an active form of STAT6, STAT6VT. Therefore, although GATA3 has been recognized as a master regulator of Th2 cell differentiation, many Th2-specific genes are not regulated by GATA3 itself but in collaboration with STAT6. Th1 and Th2 subsets are profiled for mRNA expression Examination of GATA3-binding and 3 different histone modifications in Th1 and Th2 cells.
2011-03-31 | E-GEOD-28292 | biostudies-arrayexpress
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.
2018-03-05 | GSE109107 | GEO
Project description:Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity. Mock-transfected and GATA3 siRNA-transfected Th2 and Th2-4th cells are profiled for mRNA expression
2013-04-19 | E-GEOD-46185 | biostudies-arrayexpress
Project description:Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling and increased expression of a set of Th2-specific genes including those encoding Th2 cytokines. IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression. However, it remains unclear whether the expression of other Th2-specific genes is induced directly by GATA3. A genome-wide unbiased ChIP-seq analysis revealed that GATA3 bound to 1,279 genes selectively in Th2 cells, and 101 genes in both Th1 and Th2 cells. Simultaneously, we identified 26 highly Th2-specific STAT6-dependent inducible genes by a DNA microarray analysis-based three-step selection processes, and among them 17 genes showed GATA3 binding. We assessed dependency on GATA3 for the transcription of these 26 Th2-specific genes, and 10 genes showed increased transcription in a GATA3-dependent manner while 16 genes showed no significant responses. The transcription of the 16 GATA3-nonresponding genes was clearly increased by the introduction of an active form of STAT6, STAT6VT. Therefore, although GATA3 has been recognized as a master regulator of Th2 cell differentiation, many Th2-specific genes are not regulated by GATA3 itself but in collaboration with STAT6.
2011-03-31 | GSE28292 | GEO
Project description:Purpose: To analyze the transcriptome difference of Th2 cells derived from Gata3(fl/fl) and Klrg1Cre Gata3(fl/fl) mice Method: Lung Th2 cells were used from mice chronically challenged with papain (40 µg/20 µl PBS, 6 subsequent papain challenges, day 0, 1, 2, 13, 14, and 15)
2024-02-01 | GSE166600 | GEO
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.
2018-03-05 | GSE108633 | GEO
Project description:Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.
2013-04-19 | GSE46185 | GEO
Project description:T-bet and GATA3 induce differentiation of CD4+ T-cells into Th1 or Th2 effectors. These exhibit a range of different properties but understanding of T-bet and GATA3 function is mostly limited to the murine Ifng and Il4/Il5/Il13 loci. We hypothesised that extending such analyses across the human genome would allow further insight into T-bet and GATA3 function. We have discovered that T-bet and GATA3 bind to multiple distal sites at a set of key immune regulatory genes. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with lineage-specific expression regulated by T-bet and GATA3. Our approach also reveals that GATA3 is distributed at T-bet binding sites in Th1 cells and that T-bet directly activates its own expression. We propose that these aspects of T-bet and GATA3 function are critical for Th1/ Th2 differentiation and provide a model for the relationship between other lineage-specific regulators. ChIP was performed using antibody against T-bet in Th1 cells and against GATA3 in Th1 cells as well as Th2 cells. A sample of whole cell extract (WCE) from Th1 cells and Th2 cells was sequenced. Th1 WCE was used as the background to determine enrichment.
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Project description:The type 2 helper effector program is driven by the master transcription factor GATA3 and can be expressed by subsets of both innate lymphoid cells (ILCs) and adaptive CD4+ T helper (Th) cells. While ILC2s and Th2 cells acquire their type 2 differentiation program under very different contexts, the distinct regulatory mechanisms governing this common program are only partially understood. Here we show that the differentiation of ILC2s, and their concomitant high level of GATA3 expression, are controlled by a Gata3 enhancer, Gata3 +674/762, that plays only a minimal role in Th2 cell differentiation. Mice lacking this enhancer exhibited defects in several but not all type 2 inflammatory responses, depending on the respective degree of ILC2 and Th2 cell involvement. Our study provides molecular insights into the different gene regulatory pathways leading to the acquisition of the GATA3-driven type 2 helper effector program in innate and adaptive lymphocytes.
2021-07-22 | GSE169542 | GEO
Project description:Host defense against diverse pathogens involves the recruitment and differentiation of CD4+ T effector subsets including T helper 1 (Th1), Th2, Th17 and induced regulatory T (Treg) cells. Surface phenotype studies have revealed subset-specific surface markers for the identification and purification of human primary CD4+ T effector subsets. In the present study, we aimed to characterize the mRNA and large intergenic non-coding RNA (lincRNA) expression differences between human primary CD4+ T effector subsets and identify potential subset-specific genes. To achieve this goal, mRNA and lincRNA microarray profiling of flow cytometry-sorted human primary Th1, Th2, Th17 and Treg cells was performed. Principal component and pathway analyses revealed subset-specific gene expression patterns. A Th2-specific lincRNA, GATA3-AS1, also termed FLJ45983, was identified in primary immune cells and tissues, as well as in in vitro polarized CD4+ T effector subsets. Further analysis showed that GATA3-AS1 was a potential diagnostic marker in allergy, a Th2-associated disease. This first systematic genome-wide analysis of gene expression differences between primary CD4+ T effector subsets may help to identify novel regulatory protein-coding genes and lincRNAs regulating CD4+ T cell subset differentiation, as well as potential diagnostic markers. As an example, we identified a GATA3-associated Th2-specific marker lincRNA GATA3-AS1. Gene expression microarray analysis of flow-cytometry sorted human primary naïve CD4+ T cells, CD4+ T central memory cells, Th1, Th2, Th17 and Treg cells from buffy coat of four healthy controls Gene expression microarray analysis was performed using SurePrint G3 Human Gene Expression 8X60K microarray.
2013-06-01 | E-GEOD-43005 | biostudies-arrayexpress