Opening act in a hematopoietic program.

摘要

In this issue of Blood, Hoogenkamp and colleagues describe chromatin modifications associated with activation of the hematopoietic transcription factor Pu. 1 gene in the earliest stages of blood cell production in differentiating ES cells. Surprisingly, the Runx1 transcription factor is a major but transient player required only in this opening act. Pu. 1 is a well-known pivotal factor in adult hematopoiesis. Complete deficiency of Pu. 1 results in late gestational lethality, with an absence of fetal liver granulocytes, macrophages, and B lymphocytes. The Runxl transcription factor is an upstream regulator of Pu. 1 and is required for Pu. 1 expression. Pu. 1, in turn, is pivotal for the expression of the colony-stimulating factor 1 receptor (Csfr1), which is required for macrophage differentiation. In the adult bone marrow, hematopoietic stem cells, common lymphocyte progenitors (CLPs), and common my-eloid progenitors (CMPs) all express Pu. 1. Varying levels of Pu.1 in CMPs influence cell fate decisions, with high-expressing CMPs efficient in granulocyte/macrophage differentiation and low-expressing CMPs committed to the megakaryocyte/erythroid lineage. Pu. 1 is down-regulated in the transition of CLP to the B-lymphoid lineage and is extinguished in the T-lymphoid lineage. While the Pu. 1 cis regulatory elements have been extensively characterized in vivo, due to limiting numbers of hematopoietic progenitors available in these models, no studies until now have been able to examine the epige-netic changes accompanying the onset of Pu. 1 expression. In this issue of Blood, the report by Hoogenkamp et al is the first to correlate chromatin changes in Pu. I regulatory elements with hematopoietic commitment.