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RUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913-4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.

Original publication

DOI

10.1128/MCB.05938-11

Type

Journal article

Journal

Mol Cell Biol

Publication Date

10/2012

Volume

32

Pages

3814 - 3822

Keywords

Animals, Cell Line, Tumor, Core Binding Factor Alpha 2 Subunit, DNA, Erythroid Cells, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Hematopoiesis, Histone Demethylases, Mice, Morpholinos, Multiprotein Complexes, Nerve Tissue Proteins, Oxidoreductases, N-Demethylating, Protein Binding, Repressor Proteins, Zebrafish, Zebrafish Proteins