The Runx1 transcription factor - an essential hematopoiesis regulator - is involved in several leukaemia-causing chromosomal translocations. An important route to understanding the pathology of such Runx-mediated cancers is to elucidate what controls Runx expression or stability. Philip Crosier and colleagues have now discovered, from a genetic screen in zebrafish for positive regulators of runx1, that Rad21, a cohesin subunit,regulates runx1 transcription in a dose-dependent manner. This depends on cohesin, a protein complex that is required for sister chromatid cohesion (),and is the first example of cohesin-dependent gene regulation in vertebrates. In a series of genetic and morpholino-knockdown experiments, the authors show that in zebrafish rad21 mutants, differentiated blood cells do not form and runx3 and hematopoietic runx1 expression is lost. Removing one copy of rad21 reduces runx1 and also downstream proneural gene expression. Knocking down Smc3 - another cohesin subunit -similarly reduces runx1 expression. Thus, the cohesin complex regulates runx1 expression in zebrafish, but exactly how, awaits future work.
