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

Sandberg, Mark and Sutton, Susan and Pletcher, Mathew and Wiltshire, Timothy and Tarantino, Lisa and 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
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 14:02
Last Modified: 31 Jan 2013 01:22
URI: https://oak.novartis.com/id/eprint/258

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