Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Shamit Soneji

PROVIDER: E-GEOD-49991 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

May Gillian G Soneji Shamit S Tipping Alex J AJ Teles Jose J McGowan Simon J SJ Wu Mengchu M Guo Yanping Y Fugazza Cristina C Brown John J Karlsson Göran G Pina Cristina C Olariu Victor V Taylor Stephen S Tenen Daniel G DG Peterson Carsten C Enver Tariq T

Cell stem cell 20131010 6

We used the paradigmatic GATA-PU.1 axis to explore, at the systems level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIP-seq of GATA1, GATA2, and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (1) differential complexity of sequence motifs bound by GATA1, GATA2, and PU.1; (2) the scope and interplay of GATA1 and GATA2 p ...[more]

PMID: 24120743

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Project description:Transcriptional profiling of mouse comparing in vitro-derived DC progenitors from control and Gata2 conditional knockout mice. Two-condition experiment, Control DCs vs. G2 Knockout DCs. Biological replicates: 4 control, 3 Gata2 knockout, independently grown and harvested. One replicate per array. Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germline GATA2 mutations induce GATA2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Linâ??Sca-1+Kit+ cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell fate specification toward the myeloid versus T lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation.

Dataset Information

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

Publications

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

Similar Datasets

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