Polycomb contraction differentially regulates terminal human hematopoietic differentiation programs

Abstract

Mature blood cells derive from primitive cells through a complex and poorly understood process that involves an interplay of transcription factors and epigenetic modifications. We now show that multiple human hematopoietic progenitor phenotypes display a common repressive H3K27me3 signature (R>0.97) together with their mature lymphoid, but not their differentiated monocyte and erythroid progeny. This signature includes many large organized H3K27me3 domains that we also show are required for the production of differentiating lymphoid cells. These results reveal H3K27me3 contraction to play a previously unknown intermediate step in differentially regulating the activation of terminal differentiation programs in normal human lymphoid and myeloid progenitors.