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Gene expression changes in embryonic PECAM-1+ cells from Gata2 +9.5 enhancer targeted mice

ABSTRACT: We have generated a nonconditionall deletion of an E-box - GATA motif composite element from a putative enhancer 9.5 kb downstream of the Gata2 1S promoter. The mutation results in lethality at E13.5 to E14.5 with embryos exhibiting dectects in definitive hematopoiesis and vasculature integrity. Hematopoietic stem and progenitor cells are nearly absent from these mice and Gata2 expression is severely reduced in Pecam-1+ endothelial cells from E12.5-12.5 embryos but is expressed at normal levels in the embryonic brain. We have employed gene expression profiling in Pecam-1+ cells from wild type and Gata 2+9.5 mutant littermates to identify genes involved in maintaining vascular integrity.

ORGANISM(S): Mus musculus

PROVIDER: GSE39300 | GEO | 2012/07/17

SECONDARY ACCESSION(S): PRJNA170521

REPOSITORIES: GEO

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Gene expression changes in embryonic PECAM-1+ cells from Gata2 +9.5 enhancer targeted mice

Project description:We have generated a nonconditionall deletion of an E-box - GATA motif composite element from a putative enhancer 9.5 kb downstream of the Gata2 1S promoter. The mutation results in lethality at E13.5 to E14.5 with embryos exhibiting dectects in definitive hematopoiesis and vasculature integrity. Hematopoietic stem and progenitor cells are nearly absent from these mice and Gata2 expression is severely reduced in Pecam-1+ endothelial cells from E12.5-12.5 embryos but is expressed at normal levels in the embryonic brain. We have employed gene expression profiling in Pecam-1+ cells from wild type and Gata 2+9.5 mutant littermates to identify genes involved in maintaining vascular integrity. The Gata2+9.5 mutation was backcrossed into the C57Bl/6J background. Anti-CD31 antibody bound to magnetic beads was used to enrich for PECAM-1+ cells from four Gata2+9.5 E12.5 embryos and four wild type littermates from two litters. A single RNA sample from each embryo was used for array hybridization.

2012-07-16 | E-GEOD-39300 | biostudies-arrayexpress

Mus musculus Gata2 +9.5 Ets C>T transition untreated and 10 days post 5-FU LSK cells

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Project description:Inherited or sporadic mutations in the transcription factor GATA2 have been shown to be responsible for MonoMAC syndrome, a GATA2 deficiency disease characterized by a constellation of findings including disseminated non-tuberculous mycobacterial infections, severe deficiencies of monocytes, natural killer cells, and B-lymphocytes, and myelodysplastic syndrome. Mutations in the GATA2 gene are found in ~90% of patients with a GATA2 deficiency phenotype and are largely missense mutations in the conserved second zinc-finger domain or truncation mutations elsewhere in the coding sequence. Mutations in an intron 5 regulatory enhancer element are also well described in GATA2 deficiency. Here we present a large multigeneration kindred with the clinical features of GATA2 deficiency but lacking an apparent GATA2 mutation. Whole Genome Sequencing revealed a unique Adenine-to-Thymine variant in the GATA2 -110 enhancer 116,855bp upstream of the GATA2 gene. The mutation creates a new E-box consensus in position with an existing GATA-box to generate a new hematopoietic regulatory composite element. The mutation segregates with the disease pattern in five generations of the family pedigree. Cell-type specific allelic imbalance of GATA2 expression is observed in a patient’s bone marrow with higher expression from the mutant-linked allele. Allele-specific overexpression of GATA2 is observed in CRISPR/Cas9-modified HL60 cultured cells and in luciferase assays with the enhancer mutation. This study demonstrates overexpression of GATA2 resulting from a single nucleotide change in an upstream regulatory enhancer element in patients with MonoMAC syndrome.

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Mus musculus

Project description:Gene expression changes in embryonic PECAM-1+ cells from Gata2 +9.5 enhancer targeted mice

| PRJNA170521 | ENA

Cut and run analysis in human trophoblast stem cells (CT27) upon pulling down with GATA2 and GATA3 antibody

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Pioneer factor FOXA1 defines GATA2- and AR-mediated transcriptional program in prostate cancer [gene expression]

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Mus musculus Gata2 +9.5 Ets C>T transition untreated and 10 days post 5-FU LSK cells

Project description:Mus musculus Gata2 +9.5 Ets C>T transition untreated and 10 days post 5-FU LSK cells

| PRJNA507449 | ENA