GATA Switch Enhancers Mark Dynamically Regulated Chromatin Interaction Nodes during Erythroid Maturation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE155103 | GEO | 2024/01/05
REPOSITORIES: GEO
Similar Datasets
Project description:We discovered enhancers that control GATA-2 expression during mouse development and in adult and generated mutant mouse strains that lack these enhancers, and these mice have very specific and important phenotypes that revealed GATA-2 mechanisms to control stem and progenitor cell transitions. In this study we aim to determine what proteins are under control of the GATA-2 -77 enhancer in a pool of heterogeneous blood progenitor cells with the specific focus on Socs2 expression.
2020-06-05 | PXD013855 | Pride
Project description:Human erythropoiesis is a stepwise process in which multipotent hematopoietic stem/progenitor cells (HSPC) are initially committed towards the erythroid lineage and then differentiated into mature erythroid precursors. Commitment and differentiation are tightly regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. Although the role of GATA factors in erythropoiesis has been extensively studied, how they regulate transcription from early to late stages of human erythropoiesis still remains underinvestigated. Here, we investigated GATA-mediated transcriptional regulation along erythroid development through the integrative analysis of gene expression, chromatin modifications, and GATA factors’ binding in human HSPC, early erythroid progenitors, and late precursors. A progressive loss of H3K27 acetylation, a mark of active regulatory elements, and diminished usage of active enhancers and super-enhancers was observed during erythroid lineage commitment and differentiation. We found that GATA factors mediate the transcriptional changes occurring during erythropoiesis through a stage-specific interplay with regulatory elements. In particular, GATA1 binds different sets of regulatory elements in early progenitors and late precursors, and controls the transcription of distinct genes in commitment and differentiation. By Chromosome Conformation Capture and CRISPR/Cas9-mediated genome editing, we demonstrated that the binding of GATA1 to a stage-specific super-enhancer sustains the expression of the stem cell factor receptor KIT in human erythroid progenitors. This study provides insights into the dynamics of epigenetic and transcriptional interactions during erythroid development and highlights a new layer of GATA1-mediated regulation in erythropoiesis.
2020-04-10 | GSE124164 | GEO
Project description:Human erythropoiesis is a stepwise process in which multipotent hematopoietic stem/progenitor cells (HSPC) are initially committed towards the erythroid lineage and then differentiated into mature erythroid precursors. Commitment and differentiation are tightly regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. Although the role of GATA factors in erythropoiesis has been extensively studied, how they regulate transcription from early to late stages of human erythropoiesis still remains underinvestigated. Here, we investigated GATA-mediated transcriptional regulation along erythroid development through the integrative analysis of gene expression, chromatin modifications, and GATA factors’ binding in human HSPC, early erythroid progenitors, and late precursors. A progressive loss of H3K27 acetylation, a mark of active regulatory elements, and diminished usage of active enhancers and super-enhancers was observed during erythroid lineage commitment and differentiation. We found that GATA factors mediate the transcriptional changes occurring during erythropoiesis through a stage-specific interplay with regulatory elements. In particular, GATA1 binds different sets of regulatory elements in early progenitors and late precursors, and controls the transcription of distinct genes in commitment and differentiation. By Chromosome Conformation Capture and CRISPR/Cas9-mediated genome editing, we demonstrated that the binding of GATA1 to a stage-specific super-enhancer sustains the expression of the stem cell factor receptor KIT in human erythroid progenitors. This study provides insights into the dynamics of epigenetic and transcriptional interactions during erythroid development and highlights a new layer of GATA1-mediated regulation in erythropoiesis.
2020-04-10 | GSE124163 | GEO
Project description:There are many examples of transcription factor families whose members control gene expression profiles of diverse cell types. However, the mechanism by which closely related factors occupy distinct regulatory elements and impart lineage specificity is largely undefined. Here we demonstrate on a genome wide scale that the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes, often at distinct sites, as a means to differentially regulate target gene expression and to regulate the balance between proliferation and differentiation. We also reveal that the GATA switch, which entails a chromatin occupancy exchange between GATA2 and GATA1 in the course of differentiation, operates on more than a third of GATA1 bound genes. The switch is equally likely to lead to transcriptional activation or repression and, in general, GATA1 and GATA2 act oppositely on switch target genes. In addition, we reveal that genomic regions co-occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy in erythroid cells and megakaryocytes, we find that the presence of ETS factor motifs is a major discriminator of megakaryocyte versus red cell specification.
2012-03-05 | GSE31331 | GEO
Project description:CRISPR/Cas9-mediated ablation of two Alas2 intronic cis-elements in G1E-ER-GATA1 cells strongly reduced GATA-1-induced Alas2 transcription, heme biosynthesis, and GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing Alas2 function in Alas2 cis-element-mutant (double mutant) cells by providing its catalytic product 5-aminolevulinic acid (5-ALA) rescued heme biosynthesis and a subset of GATA-1-dependent genetic network. Using the same system, we discovered a GATA-1- and heme-dependent circuit that regulates chromatin accessibility during erythroid maturation.
2018-05-30 | GSE114996 | GEO
Project description:We explored the role of FOG-1 in GATA-1 transcriptional regulation of megakaryocyte differentiation through expression of wild-type GATA-1 and the FOG-binding mutant of GATA-1 (GATA-1^V205G) in G1ME cells. G1ME cells were derived from Gata1-null mouse ES cells and have both megakaryocyte and erythrocyte differentiation potential upon reconstitution of GATA-1 expression (Stachura 2006). HA-tagged wild-type or mutant GATA-1 were expressed in G1ME cells grown in TPO via retroviral transductions. The cells were sorted for GFP positivity 68 hours post-transduction and then were allowed to recover in normal growth medium for 4h. Total RNA was then isolated using RNeasy kit from Qiagen 72 hours post-transduction.
2012-03-05 | E-GEOD-35695 | biostudies-arrayexpress
Project description:We report ChIP-Seq data for GATA-1 and the FOG-binding mutant of GATA-1 (GATA-1^V205G) in G1ME cells, a Gata1-null cell line with both erythroid and megakaryocytic differentiation potential. We introduced HA-tagged GATA-1 or V205G into G1ME cells via retroviral transduction. The cells were crosslinked at 48h post-transduction, and an HA antibody was used for chromatin immunoprecipitation (ChIP). ChIP and input samples were sequenced on Illumina GAII high-throughput sequencer. The data reveal GATA-1-specific and V205G-specific bidning sites, indicating that FOG-1 both faacilitates and prohibits GATA-1 chromatin occupancy in a context-dependent manner. Examinaton of chromatin occupancy of GATA-1 anda FOG-binding mutant of GATA-1 in G1ME cells cultured in TPO.
2012-07-30 | E-GEOD-35644 | biostudies-arrayexpress
Project description:We report ChIP-Seq data for GATA-1 and the FOG-binding mutant of GATA-1 (GATA-1^V205G) in G1ME cells, a Gata1-null cell line with both erythroid and megakaryocytic differentiation potential. We introduced HA-tagged GATA-1 or V205G into G1ME cells via retroviral transduction. The cells were crosslinked at 48h post-transduction, and an HA antibody was used for chromatin immunoprecipitation (ChIP). ChIP and input samples were sequenced on Illumina GAII high-throughput sequencer. The data reveal GATA-1-specific and V205G-specific bidning sites, indicating that FOG-1 both faacilitates and prohibits GATA-1 chromatin occupancy in a context-dependent manner.
2012-07-30 | GSE35644 | GEO
Project description:There are many examples of transcription factor families whose members control gene expression profiles of diverse cell types. However, the mechanism by which closely related factors occupy distinct regulatory elements and impart lineage specificity is largely undefined. Here we demonstrate on a genome wide scale that the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes, often at distinct sites, as a means to differentially regulate target gene expression and to regulate the balance between proliferation and differentiation. We also reveal that the GATA switch, which entails a chromatin occupancy exchange between GATA2 and GATA1 in the course of differentiation, operates on more than a third of GATA1 bound genes. The switch is equally likely to lead to transcriptional activation or repression and, in general, GATA1 and GATA2 act oppositely on switch target genes. In addition, we reveal that genomic regions co-occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy in erythroid cells and megakaryocytes, we find that the presence of ETS factor motifs is a major discriminator of megakaryocyte versus red cell specification. We used Illumina ChIP-Seq to examine binding of GATA1, GATA2, and ETS1 transcription factors as well as the genomic locations of two histone methylation marks, H3K4me3 and H3K27me3. Except H3K4me3 (1 sample), all data were generated from at least 2 biological replicates of immunoprecipitations from megakaryocyte progenitor cells, G1ME. Input DNA was prepared and sequenced along with each immunoprecipitation and used as a control dataset for binding site identification.
2012-03-05 | E-GEOD-31331 | biostudies-arrayexpress
Project description:GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Examination of GATA1 and GATA2 occpancy in K562 cells
2009-11-25 | E-GEOD-18868 | biostudies-arrayexpress