The mixed lineage leukemia (MLL) gene was well known for its recurrent chromosomal translocation with more than 70 partner genes leading to acute myeloid leukemias (AML) and acute lymphoblastic leukemia (ALL). In mammalians, Mll encodes a histone methyltransferase, which maintains homeobox (Hox) gene expression through epigenetic regulation. As Mll-knockout mice are early embryonic lethal, its function during early embryogenesis remains unclear. 

Recently, Dr. Xiaoyang Wan from the Research Group of Molecular Toxicology (Principal Investigator: Prof. Xiao Wuhan) at Institute of Hydrobiology (IHB) analyzed the role of mll in early embryogenesis using zebrafish model. They found that mll was essential for haematopoiesis, because mll knocking down by morpholinos significantly reduced the expression of hematopoietic progenitor markers as well as blood cells. In addition, although Mll depletion sharply down-regulated hox gene expression as same as that in mammalians, over-espression by hox gene could not fully rescue the hematopoietic defects. This indicated that other genes might also be involved in the process of haematopoiesis manipulated by Mll. 

Furthermore, they indentified a candidate target gene suppressed by MLL in zebrafish-Gadd45αa through microarray analysis. Exotic expression of Gadd45αa could mimic the hematopoietic deficient phenotypes caused by Mll depletion. Further studies proved that double knocking down of Gadd45αa and Mll could partially restore the expression level of blood cell markers. Thus Mll might regulate Gadd45αa to mediate haematopoiesis. 

This research has been published on line in Journal of Biological Chemistry on July 22. The work was supported by Major State Basic Research Development Program (973), National Natural Science Foundation and Science Foundation of the Chinese Academy of Sciences.