Precise control of GATA3 expression in CD4+ T cell differentiation via selective activation of primed enhancers
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE190860 | GEO | 2023/02/24
REPOSITORIES: GEO
Similar Datasets
Project description:Precise control of GATA3 expression in CD4+ T cell differentiation via selective activation of primed enhancers
| PRJNA788758 | ENA
Project description:Estrogen Receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1, contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1 co-operating transcription factor mutated in breast tumors, however its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of co-factors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1 binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3 mediated re-distribution of ESR1 binding. The GATA3-mediated re-distributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1 bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen- ESR1 mediated interactions between cis-regulatory elements. Together these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer. GATA and ER binding studied by chromatin immunoprecipitation in breast cancer cell lines, with and without estrogen stimulation and by knocking down GATA
2012-11-26 | E-GEOD-40129 | biostudies-arrayexpress
Project description:Estrogen Receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1, contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1 co-operating transcription factor mutated in breast tumors, however its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of co-factors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1 binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3 mediated re-distribution of ESR1 binding. The GATA3-mediated re-distributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1 bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen- ESR1 mediated interactions between cis-regulatory elements. Together these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer. MCF7 cells were transfected with siRNA and cultured in hormone deprived conditions for a further 3 days. Cells were subsequently treated with 100nM estrogen (E2) or control (Veh) for 6 hrs. We performed two independent biological experiments each using three different siRNAs against GATA3 individually (six siGATA3 replicates in total). For siControl we used RNA from five biological replicates.
2012-11-26 | E-GEOD-39623 | biostudies-arrayexpress
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.
2012-11-16 | E-GEOD-31320 | biostudies-arrayexpress
Project description:Estrogen Receptor (ER) is a steroid hormone receptor that regulates epithelial genes in breast cancer. ER forms a regulatory network with the other transcription factors, FOXA1 and GATA3. GATA3 is known to be capable of specifying chromatin localization of FOXA1 and ER. GATA3 has been identified as one of the most frequently mutated genes in breast cancer. However, how GATA3 mutations impact this transcriptional network is unknown. Here we investigate the function of one of the recurrent patient-derived GATA3 mutations (R330fs) for this regulatory network. Genomic analysis indicates that the R330fs mutant can disrupt the cooperative action of ER, FOXA1, and GATA3, and induce chromatin relocalization of these factors. Relocalizations of ER and FOXA1 are associated with altered chromatin architectures leading to differential gene expression in the GATA3 mutant cells. These results suggest the active role of GATA3 mutants in ER positive breast tumors.
2020-02-27 | GSE130703 | GEO
Project description:Estrogen Receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1, contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1 co-operating transcription factor mutated in breast tumors, however its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of co-factors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1 binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3 mediated re-distribution of ESR1 binding. The GATA3-mediated re-distributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1 bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen- ESR1 mediated interactions between cis-regulatory elements. Together these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer.
2012-11-26 | GSE40129 | GEO
Project description:Estrogen Receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1, contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1 co-operating transcription factor mutated in breast tumors, however its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of co-factors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1 binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3 mediated re-distribution of ESR1 binding. The GATA3-mediated re-distributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1 bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen- ESR1 mediated interactions between cis-regulatory elements. Together these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer.
2012-11-26 | GSE39623 | GEO
Project description:The mechanistic details by which pioneer transcription factors interact with partner transcription factors and chromatin modification/remodeling enzymes to activate enhancers remains an emerging area of study. Here, we utilize inducible expression of the pioneer factor GATA3 and study cofactor association and structural alterations in local chromatin. ATAC-seq analysis and footprinting revealed co-occurrence of GATA3 with other transcription factors, including AP-1, in newly accessible chromatin. GATA3 and AP-1 co-localize at primed enhancers with p300 and BRG1 where nucleosome positioning is responsive to GATA3 location, not to AP-1. Genetic inhibition of AP-1 binding alters chromatin opening at some, but not most, GATA3-bound loci. Pharmacologic inhibition of SWI/SNF ATPase function results in loss of GATA3-dependent chromatin accessibility, binding, and alterations in local chromatin architecture. We conclude that GATA3-dependent gains in chromatin accessibility require chromatin remodeling and that accessibility at some loci is facilitated by a partner transcription factor, in this case AP-1.
2025-06-16 | GSE280701 | GEO
Project description:The mechanistic details by which pioneer transcription factors interact with partner transcription factors and chromatin modification/remodeling enzymes to activate enhancers remains an emerging area of study. Here, we utilize inducible expression of the pioneer factor GATA3 and study cofactor association and structural alterations in local chromatin. ATAC-seq analysis and footprinting revealed co-occurrence of GATA3 with other transcription factors, including AP-1, in newly accessible chromatin. GATA3 and AP-1 co-localize at primed enhancers with p300 and BRG1 where nucleosome positioning is responsive to GATA3 location, not to AP-1. Genetic inhibition of AP-1 binding alters chromatin opening at some, but not most, GATA3-bound loci. Pharmacologic inhibition of SWI/SNF ATPase function results in loss of GATA3-dependent chromatin accessibility, binding, and alterations in local chromatin architecture. We conclude that GATA3-dependent gains in chromatin accessibility require chromatin remodeling and that accessibility at some loci is facilitated by a partner transcription factor, in this case AP-1.
2025-06-16 | GSE280565 | GEO
Project description:The mechanistic details by which pioneer transcription factors interact with partner transcription factors and chromatin modification/remodeling enzymes to activate enhancers remains an emerging area of study. Here, we utilize inducible expression of the pioneer factor GATA3 and study cofactor association and structural alterations in local chromatin. ATAC-seq analysis and footprinting revealed co-occurrence of GATA3 with other transcription factors, including AP-1, in newly accessible chromatin. GATA3 and AP-1 co-localize at primed enhancers with p300 and BRG1 where nucleosome positioning is responsive to GATA3 location, not to AP-1. Genetic inhibition of AP-1 binding alters chromatin opening at some, but not most, GATA3-bound loci. Pharmacologic inhibition of SWI/SNF ATPase function results in loss of GATA3-dependent chromatin accessibility, binding, and alterations in local chromatin architecture. We conclude that GATA3-dependent gains in chromatin accessibility require chromatin remodeling and that accessibility at some loci is facilitated by a partner transcription factor, in this case AP-1.
2025-06-16 | GSE280704 | GEO