Open AccessDistinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal
Author(s) -
Vivienne I. Rebel,
Andrew L. Kung,
E Tanner,
Hong Yang,
Roderick T. Bronson,
David M. Livingston
Publication year - 2002
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.232568499
Subject(s) - haematopoiesis , stem cell , creb , biology , hematopoietic stem cell , creb binding protein , microbiology and biotechnology , transcription factor , carcinogenesis , cancer research , genetics , cancer , gene
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.