GATA2 is a master regulator of the formation and development of hematopoietic stem/progenitor cells (HSPCs), which form the various types of blood cells. Dysregulation of GATA2 has been linked to several different human disease states, including leukemia, and MonoMAC and Emberger syndromes.
In this issue of the Journal of Clinical Investigation two research groups report on genetic regulatory elements that profoundly alter the expression and activity of GATA2. James Douglas Engel and colleagues at the University of Michigan disrupted GATA2 expression in the endothelial tissue of mice, which resulted in embryonic lethality that was attributed to the loss of liver HSPCs and defective lymphatic vasculature development.
Researchers led by Emery Bresnick at the University of Wisconsin at Madison identified a new mutation in a GATA2 genetic regulatory element in a MonoMAC patient. Deletion of this regulatory element in mice caused embryonic lethality that was also linked to depletion of liver HSPCs and a loss of vascular integrity. Both of these studies underscore the role of GATA2 in vascular integrity and may help define the pathology of GATA2-associated human diseases.
“Conditional GATA2 inactivation results in HSC loss and lymphatic mispatterning” James Engel
The University of Michigan Medical Schoolool, Ann Arbor, MI, USA
“Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity”
University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Journal of Clinical Investigation Sept. 10, 2012