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Genome-wide analysis of GATA1, GATA2, RUNX1, FLI1 and SCL binding in primary human megakaryocytes

ABSTRACT: We have mapped the binding sites for the five key regulators GATA1, GATA2, RUNX1, FLI1 and TAL1/SCL in primary human megakaryocytes. Statistical analysis identified subsets of enriched as well as depleted combinatorial binding patterns. In particular simultaneous binding by all 5 factors was highly enriched and occurred in the vicinity of many genes known to be involved in blood and megakaryocyte development. Knock down in zebrafish of 8 of these genes with no previously known role in hematopoiesis, revealed all to be essential for thrombocyte and/or erythroid development. Combinatorial analysis of multi-factor ChIP-Seq datasets coupled with a high-throughput in vivo screen therefore offers a powerful strategy to identify novel essential regulators of complex mammalian differentiation processes. 5 transcription factors and rabbit-IgG in megakaryocytes.

ORGANISM(S): Homo sapiens  

SUBMITTER: Dana C Bellissimo   Berthold Gottgens  Willem H Ouwehand  Ana Cvejic  Marloes R Tijssen  Rebecca L Hannah  Xiaonan Wang  Samuel David Foster  Anagha Joshi 

PROVIDER: E-GEOD-24674 | ArrayExpress | 2011-06-01



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Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development of individual lineages. Here, we report the genome-wide binding sites for the five key hematopoietic transcription factors--GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL--in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous binding by all five factors was the most enriched pattern and often occurred  ...[more]

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