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

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Animal, Blastocyst, Cell-Culture, Cell-Differentiation, Cell-Division, Cell-Line, Crosses-Genetic, DNA-Binding-Protein-Cyclic-AMP-Responsive, Hematologic-Neoplasms, Hematopoietic-Stem-Cells, Mice, Mice-Inbred-C57BL, Mice-Knockout, Nuclear-Proteins, Sequence-Deletion, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Trans-Activators

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Proc Natl Acad Sci USA 2002 Nov; 99(23):14789-94


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.