Epigenetic regulations in hematopoietic Hox code

Hox genes encode DNA-binding proteins that are deployed in overlapping domains along various body axes during embryonic development. This sequential activation of Hox genes in temporal and spatial mode, the Hox code, is critical for the proper positioning of segmented structures along those axes, which include the vertebrate, limbs and, also digestive and reproductive tracts. It remains unknown how Hox genes are regulated to determine the identity of hematopoietic stem cells and their derivatives, which migrate and express most Hox genes. The key questions are whether the hematopoietic system has an axis, how epigenetic mechanisms restrict expression of Hox genes to specific cell types and what role Hox genes play in leukemic transformation? Taking in account these questions, we propose a combinatorial axial model of hematopoietic Hox code to predict the positional identity of the hematopoietic cells. This model will provide new insight into epigenetic therapy in leukemia. Oncogene (2011) 30, 379-388; doi:10.1038/onc.2010.484; published online 25 October 2010