Differential gene regulation by the disease-associated short isoform of GATA1 (microarray)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64494 | GEO | 2015/02/04
SECONDARY ACCESSION(S): PRJNA271111
REPOSITORIES: GEO
Similar Datasets
Project description:The transcriptional activiy of GATA1s was compared to GATA1 through gene expression analysis in a cell line model with both erythroid and megakaryocyte differentiation. G1ME cells were derived from Gata1- mouse ES cells and have both megakaryocyte and erythrocyte differentiation potential upon reconstitution of GATA-1 expression (Stachura 2006). HA-tagged full length or short 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.
2015-02-04 | E-GEOD-64494 | biostudies-arrayexpress
Project description:We report ChIP-Seq data for GATA1 and the leukemia-associated short isoform GATA1s in G1ME cells, a Gata1-null cell line with both erythroid and megakaryocytic differentiation potential. We introduced HA-tagged GATA1 or GATA1s 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 or GAIIx high-throughput sequencers. The data reveal a deficiency of chromatin occupancy by GATA1s, especially at genes involved in erythrocyte differentiation and function.
2015-02-04 | GSE64327 | GEO
Project description:We report ChIP-Seq data for GATA1 and the leukemia-associated short isoform GATA1s in G1ME cells, a Gata1-null cell line with both erythroid and megakaryocytic differentiation potential. We introduced HA-tagged GATA1 or GATA1s 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 or GAIIx high-throughput sequencers. The data reveal a deficiency of chromatin occupancy by GATA1s, especially at genes involved in erythrocyte differentiation and function. Examinaton of chromatin occupancy of GATA1 and GATA1s in G1ME cells cultured in TPO.
2015-02-04 | E-GEOD-64327 | biostudies-arrayexpress
Project description:We transduced mouse Gata1- megakaryocyte-erythroid progenitors with MIGRI-GFP vector expressing GATA1fl or GATA1s cDNAs. GFP-positive cells expressing one of the two isoforms of GATA1 were isolated by FACS 42 hours following transduction and used for microarray transcriptome analysis. At this time point, there was no apparent difference in the cell surface phenotypes between GATA1fl and GATA1s-expressing cells. Transcriptome data for G1ME/GATA1fl at 42h were deposited previously under GSE14980 (GSM374049, GSM374050, GSM374051), whereas G1ME/GATA1s at 42h are deposited here.
2015-01-26 | GSE62879 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Germline GATA1 mutations resulting in the production of an amino-truncated protein termed GATA1s (for “short”) cause congenital hypoplastic anemia. Similar somatic mutations promote transient myeloproliferative disease and acute megakaryoblastic leukemia in trisomy 21 patients. Here we show that induced pluripotent stem cells (iPSCs) from patients with GATA1-truncating mutations exhibit impaired erythroid potential but enhanced megakaryopoiesis and myelopoiesis, faithfully recapitulating the major phenotypes of associated diseases. Similarly, GATA1s promotes megakaryopoiesis but not erythropoiesis in developmentally arrested Gata1- murine megakaryocyte-erythroid progenitors derived from murine embryonic stem cells (ESCs). Transcriptome studies demonstrate a selective deficiency in the ability of GATA1s to activate erythroid-expressed genes within populations of hematopoietic progenitors. Although its DNA binding domain is intact, chromatin immunoprecipitation studies show that GATA1s binding at specific erythroid regulatory regions is impaired, while binding at many non-erythroid sites, including megakaryocytic and myeloid target genes, is normal. These observations point to lineage specific GATA1 co-factor associations essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. More broadly, our studies underscore the value of ESCs and iPSCs to recapitulate and study disease phenotypes.
2015-01-26 | GSE61933 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Germline GATA1 mutations resulting in the production of an amino-truncated protein termed GATA1s (for M-bM-^@M-^\shortM-bM-^@M-^]) cause congenital hypoplastic anemia. Similar somatic mutations promote transient myeloproliferative disease and acute megakaryoblastic leukemia in trisomy 21 patients. Here we show that induced pluripotent stem cells (iPSCs) from patients with GATA1-truncating mutations exhibit impaired erythroid potential but enhanced megakaryopoiesis and myelopoiesis, faithfully recapitulating the major phenotypes of associated diseases. Similarly, GATA1s promotes megakaryopoiesis but not erythropoiesis in developmentally arrested Gata1- murine megakaryocyte-erythroid progenitors derived from murine embryonic stem cells (ESCs). Transcriptome studies demonstrate a selective deficiency in the ability of GATA1s to activate erythroid-expressed genes within populations of hematopoietic progenitors. Although its DNA binding domain is intact, chromatin immunoprecipitation studies show that GATA1s binding at specific erythroid regulatory regions is impaired, while binding at many non-erythroid sites, including megakaryocytic and myeloid target genes, is normal. These observations point to lineage specific GATA1 co-factor associations essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. More broadly, our studies underscore the value of ESCs and iPSCs to recapitulate and study disease phenotypes. Refer to individual Series
2015-01-26 | E-GEOD-61933 | biostudies-arrayexpress
Project description:We transduced mouse Gata1- megakaryocyte-erythroid progenitors with MIGRI-GFP vector expressing GATA1fl or GATA1s cDNAs. GFP-positive cells expressing one of the two isoforms of GATA1 were isolated by FACS 42 hours following transduction and used for microarray transcriptome analysis. At this time point, there was no apparent difference in the cell surface phenotypes between GATA1fl and GATA1s-expressing cells. Transcriptome data for G1ME/GATA1fl at 42h were deposited previously under GSE14980 (GSM374049, GSM374050, GSM374051), whereas G1ME/GATA1s at 42h are deposited here. We performed differential expression analysis comparing mean expression levels of genes in G1ME cells at 42 hours after transduction with GATA1fl (3 replicates deposited previously under GSE14980: GSM374049, GSM374050, GSM374051) or GATA1s (3 replicates deposited here). All 6 samples were prepared the same way and analyzed on the same platform, Affymetrix Mouse Genome 420 2.0.
2015-01-26 | E-GEOD-62879 | biostudies-arrayexpress
Project description:Mutations in GATA1, which lead to expression of the GATA1s isoform that lacks the GATA1 N-terminus, are seen in patients with Diamond-Blackfan Anemia (DBA). In our efforts to better understand the connection between GATA1s and DBA, we comprehensively studied erythropoiesis in Gata1s mice. Defects in yolks sac and fetal liver hematopoiesis included impaired terminal maturation and reduced numbers of erythroid progenitors. RNA-sequencing revealed that both erythroid and megakaryocytic genes were altered by the loss of the N-terminus, including aberrant up-regulation of Gata2 and Runx1. Mass spectrometry studies demonstrated there was a global increase in H3K27 methylation in the erythroid progenitors. By contrast, chromatin biding assays revealed that, despite similar occupancy of GATA1 and GATA1s, there was a striking reduction of H3K27me3 at regulatory elements of the Gata2 and Runx1 genes. Consistent with the observation that overexpression of GATA2 has been reported to impair erythropoiesis, we found that haploinsufficiency of Gata2 rescued the erythroid defects of Gata1s fetuses. Together, our integrated genomic analysis of transcriptomic and epigenetic signatures reveals that, although Gata1s mice do not precisely model DBA, they provide novel insights into the role of the N-terminus of GATA1 in transcriptional regulation and red blood cell maturation.
2020-04-14 | GSE130156 | GEO
Project description:We used chromatin immunoprecipitation sequencing (ChIP-seq) to compare genome-wide binding profiles of GATA1fl and GATA1s in G1ME cells, which are immortalized, developmentally arrested megakaryocyte-erythroid progenitors (MEPs) derived from in vitro differentiation of murine Gata1- ES cells. Although the truncation in GATA1s leaves the DNA binding domain intact, GATA1s fails to broadly occupy erythroid specific regulatory regions. These observations point to lineage specific co-factor associations essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease.
2015-01-26 | GSE61932 | GEO
Project description:We used chromatin immunoprecipitation sequencing (ChIP-seq) to compare genome-wide binding profiles of GATA1fl and GATA1s in G1ME cells, which are immortalized, developmentally arrested megakaryocyte-erythroid progenitors (MEPs) derived from in vitro differentiation of murine Gata1- ES cells. Although the truncation in GATA1s leaves the DNA binding domain intact, GATA1s fails to broadly occupy erythroid specific regulatory regions. These observations point to lineage specific co-factor associations essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. We performed ChIP-seq on G1ME cells 42 hours after retroviral transfer of HA-tagged full-length GATA1 (GATA1fl) or GATA1s cDNAs (2 replicates each). At this time point, there was no apparent difference in the cell surface phenotypes between GATA1fl and GATA1s-expressing cells. For each ChIP-seq replicate we obtained a matching input sample (non-ChIP DNA) as a control.
2015-01-26 | E-GEOD-61932 | biostudies-arrayexpress