c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation.

Precise control of hematopoietic stem cell (HSC) proliferation and differentiation is needed to maintain a lifetime supply of blood cells. Using genome-wide ENU mutagenesis and phenotypic screening, we have identified a mouse line that harbors a point mutation in the transactivation (TA) domain of the transcription factor c-Myb (M303V), which ...
reduces c-Myb-dependent TA by disrupting its interaction with the transcriptional coactivator p300. The biological consequences of the c-Myb(M303V/M303V) mutation include thrombocytosis, megakaryocytosis, anemia, lymphopenia, and the absence of eosinophils. Detailed analysis of hematopoiesis in c-Myb(M303V/M303V) mice reveals distinct blocks in T cell, B cell, and red blood cell development, as well as a remarkable 10-fold increase in the number of HSCs. Cell cycle analyses show that twice as many HSCs from c-Myb(M303V/M303V) animals are actively cycling. Thus c-Myb, through interaction with p300, controls the proliferation and differentiation of hematopoietic stem and progenitor cells.
Mesh Terms:
Animals, B-Lymphocytes, Base Sequence, Cell Differentiation, Cell Proliferation, DNA, E1A-Associated p300 Protein, Female, Genes, myb, Hematopoiesis, Hematopoietic Stem Cells, Male, Megakaryocytes, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Biological, Nuclear Proteins, Phenotype, Point Mutation, Protein Structure, Tertiary, Proto-Oncogene Proteins c-myb, T-Lymphocytes, Thrombocytosis, Trans-Activators, Transcriptional Activation
Dev. Cell
Date: Feb. 01, 2005
Download Curated Data For This Publication
149188
Switch View:
  • Interactions 1