Gene Set: HUANG_GATA2_TARGETS_DN

Standard name HUANG_GATA2_TARGETS_DN
Systematic name M2439
Brief description Genes down-regulated in G1ME cells (megakaryocyte/erythroid progenitor lacking GATA1 [GeneID=2623]) upon knockdown of GATA2 [GeneID=2624] by RNAi.
Full description or abstract GATA-2 is an essential transcription factor that regulates multiple aspects of hematopoiesis. Dysregulation of GATA-2 is a hallmark of acute megakaryoblastic leukemia in children with Down syndrome, a malignancy that is defined by the combination of trisomy 21 and a GATA1 mutation. Here, we show that GATA-2 is required for normal megakaryocyte development as well as aberrant megakaryopoiesis in Gata1 mutant cells. Furthermore, we demonstrate that GATA-2 indirectly controls cell cycle progression in GATA-1-deficient megakaryocytes. Genome-wide microarray analysis and chromatin immunoprecipitation studies revealed that GATA-2 regulates a wide set of genes, including cell cycle regulators and megakaryocyte-specific genes. Surprisingly, GATA-2 also negatively regulates the expression of crucial myeloid transcription factors, such as Sfpi1 and Cebpa. In the absence of GATA-1, GATA-2 prevents induction of a latent myeloid gene expression program. Thus, GATA-2 contributes to cell cycle progression and the maintenance of megakaryocyte identity of GATA-1-deficient cells, including GATA-1s-expressing fetal megakaryocyte progenitors. Moreover, our data reveal that overexpression of GATA-2 facilitates aberrant megakaryopoiesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19620289   Authors: Huang Z,Dore LC,Li Z,Orkin SH,Feng G,Lin S,Crispino JD
Exact source Table 2S: Differentially downregulated genes
Related gene sets (show 1 additional gene sets from the source publication)

(show 29 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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