A novel complex, RUNX1- MYEF2, represses hematopoietic genes in erythroid cells.

RUNX1 is known to be an essential transcription factor to generate 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 (25) in erythroid cells. Here a tagging strategy was used 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, while LSD1 is bound in differentiated cells. ChIP-seq analysis and microarray expression analysis were used to show that RUNX1 binds approximately nine thousand 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. Knock down of Myef2 expression in developing zebrafish results in a reduced number of HSC.