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Ernst, P, Mabon, M, Davidson, AJ, Zon, LI and Korsmeyer, SJ (2004) An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr. Biol. 14:2063-9


Chromosomal translocations disrupting the Mixed lineage leukemia (Mll) gene result in leukemia, with aberrant expression of some native Mll target genes (reviewed in). The Mll gene encodes a Trithorax-group chromatin regulator that is essential for the development of hematopoietic stem cells (HSCs) during embryogenesis. Like Trithorax, MLL positively regulates clustered homeodomain or Hox genes, yet the role of Hox genes collectively in the development of the mammalian hematopoietic system has been difficult to ascertain because of redundancy among Hox paralogs. Here, we show that in the absence of MLL, early hematopoietic progenitors develop despite reduced expression of HoxA, HoxB, and HoxC genes. However, these progenitors exhibit a marked reduction in their ability to generate hematopoietic colonies, a subsequent process requiring cell division and differentiation. Reactivation of a subset of Hox genes or, remarkably, reexpression of a single Hox gene in Mll-deficient progenitors rescued hematopoietic-colony frequency and growth. In contrast, expression of other MLL target genes such as Pitx2 or expression of anti-apoptotic BCL-2 failed to rescue hematopoietic-colony frequency. Furthermore, our results highlight a shared function of Hox proteins at this point in the development of the hematopoietic system.


PubMed Online version:10.1016/j.cub.2004.11.012


Cells, Cultured; DNA-Binding Proteins/metabolism; Embryo, Mammalian/cytology; Flow Cytometry; Gene Expression Regulation, Developmental; Gene Transfer Techniques; Genes, Homeobox/genetics; Hematopoiesis/genetics; Hematopoiesis/physiology; Hematopoietic Stem Cells/metabolism; Humans; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogenes; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors/metabolism



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0060216: definitive hemopoiesis



Figure 2C shows the failure of MII-deficient cells to give rise to hematopoietic colonies. Figure 2 A and B shows the normal development of cells for MII and MII-deficient cells, indicating normal differentiation. Thus, MII-deficient cells develop normally until hematopoietic differentiation. The lack of differentiation results in a failure to develop a hematopoietic center in the body.

CACAO 4421



GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion


Seeded From UniProt


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