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Transcription factor GATA1 is dispensable for mast cell differentiation in adult mice

ABSTRACT: The zinc finger transcription factor GATA1 plays an essential role for differentiation in several hematopoietic cell lineages including erythroid cells, megakaryocytes and eosinophils. Although some studies demonstrated that GATA1 is also required for mast cell differentiation, the effect of complete ablation of GATA1 in mast cell differentiation has not been examined. Here, by using tamoxifen-inducible conditional Gata1 knockout mice, we show that the role of GATA1 in mast cell differentiation is less than previously anticipated in adult mice. Although systemic administration of tamoxifen resulted in complete ablation of GATA1 protein in bone marrow and spleen, cell number and distribution of peripheral tissue mast cells in Gata1-null mice were comparable to those in wild type mice. Bone marrow cells derived from Gata1-null mice differentiated into mast cells that express both c-Kit and IgE receptor α subunit. Finally, we show a line of evidence that GATA1 and GATA2 cooperatively regulate the expression of several mast cell-specific genes by chromatin immunoprecipitation assays and quantitative RT-PCR analyses. These results indicate that GATA1 is dispensable for differentiation and maintenance of mast cells in postnatal hematopoiesis and the loss of GATA1 function is likely compensated by GATA2.

ORGANISM(S): Mus musculus

PROVIDER: GSE52254 | GEO | 2014/03/02

SECONDARY ACCESSION(S): PRJNA227282

REPOSITORIES: GEO

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Transcription factor GATA1 is dispensable for mast cell differentiation in adult mice

Project description:The zinc finger transcription factor GATA1 plays an essential role for differentiation in several hematopoietic cell lineages including erythroid cells, megakaryocytes and eosinophils. Although some studies demonstrated that GATA1 is also required for mast cell differentiation, the effect of complete ablation of GATA1 in mast cell differentiation has not been examined. Here, by using tamoxifen-inducible conditional Gata1 knockout mice, we show that the role of GATA1 in mast cell differentiation is less than previously anticipated in adult mice. Although systemic administration of tamoxifen resulted in complete ablation of GATA1 protein in bone marrow and spleen, cell number and distribution of peripheral tissue mast cells in Gata1-null mice were comparable to those in wild type mice. Bone marrow cells derived from Gata1-null mice differentiated into mast cells that express both c-Kit and IgE receptor M-NM-1 subunit. Finally, we show a line of evidence that GATA1 and GATA2 cooperatively regulate the expression of several mast cell-specific genes by chromatin immunoprecipitation assays and quantitative RT-PCR analyses. These results indicate that GATA1 is dispensable for differentiation and maintenance of mast cells in postnatal hematopoiesis and the loss of GATA1 function is likely compensated by GATA2. Murine bone marrow-derived mast cells from C57BL/6 mice were transfected with of control or GATA1 siRNA (200 pmol). Two samples were analyzed. Sample1 (ctrsi-mix) is prepared from cells transfected with control siRNA. Sample2 (G1si-mix) is prepared from cells transfected with GATA1 siRNA. For each siRNA treatment, two replicate samples prepared from different animals were pooled and used for the analysis.

2014-03-02 | E-GEOD-52254 | biostudies-arrayexpress

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Project description:We used the paradigmatic 'GATA-PU.1 axis’ to explore, at systems-level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIPSeq of GATA1, GATA2 and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (i) differential complexity of sequence motifs bound by GATA1, GATA2 and PU.1; (ii) the scope and interplay of the GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (iii) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression and (iv) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry. This 'rubric' exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis. We examine binding of three factors Gata1, Gata2 and Pu1 at 3 stages of differentiation (multipotential, 5 days of erytroid and neutrophil) , while looking at 2 intermeditate stages of erythroid differentiation for factors Gata2 and Gata1. We also look at Gata2 and Gata1 binding after Gata1 induction using an ER fusion protein.

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Mus musculus

Project description:Transcription factor GATA1 is dispensable for mast cell differentiation in adult mice

| PRJNA227282 | ENA

Dynamic analysis of gene expression and genome wide transcription factor binding during lineage-specification of multipotent progenitors [HP]

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