Sandberg, Mark, Sutton, Susan, Pletcher, Mathew, Wiltshire, Timothy, Tarantino, Lisa, Hogenesch, John and Cooke, Michael (2005) c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation. Developmental Cell, 8 (2). pp. 153-166. ISSN 1534-5807

Abstract

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
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Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 14:02
Last Modified:	31 Jan 2013 01:22
URI:	https://oak.novartis.com/id/eprint/258