Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal.

Rebel, Vivienne I; Kung, Andrew L; Tanner, Elizabeth A; Yang, Hong; Bronson, Roderick T; Livingston, David M · Proc Natl Acad Sci U S A · 2002

basic_science · Level V

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Abstract

Hematopoietic stem cells (HSC) are tightly regulated through, as yet, undefined mechanisms that balance self-renewal and differentiation. We have identified a role for the transcriptional coactivators CREB-binding protein (CBP) and p300 in such HSC fate decisions. A full dose of CBP, but not p300, is crucial for HSC self-renewal. Conversely, p300, but not CBP, is essential for proper hematopoietic differentiation. Furthermore, in chimeric mice, hematologic malignancies emerged from both CBP(-/-) and p300(-/-) cell populations. Thus, CBP and p300 play essential but distinct roles in maintaining normal hematopoiesis, and, in mice, both are required for preventing hematologic tumorigenesis.

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