Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal.
Document Type
Article
Publication Date
2002
Keywords
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
First Page
14789
Last Page
14794
JAX Source
Proc Natl Acad Sci USA 2002 Nov; 99(23):14789-94
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.
Recommended Citation
Rebel VI,
Kung AL,
Tanner EA,
Yang H,
Bronson RT,
Livingston DM.
Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal. Proc Natl Acad Sci USA 2002 Nov; 99(23):14789-94