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PMID: 12397173 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 23 ·2002-11-12 ·Pages 14789-94

Rebel VI, Kung AL, Tanner EA, Yang H, Bronson RT, Livingston DM

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.

MeSH Terms
Alleles Animals Blastocyst/cytology CREB-Binding Protein Cell Culture Techniques/methods Cell Differentiation Cell Division Cell Line Crosses, Genetic Cyclic AMP Response Element-Binding Protein/genetics,metabolism E1A-Associated p300 Protein Hematologic Neoplasms/prevention & control Hematopoietic Stem Cells/cytology Mice Mice, Inbred C57BL Mice, Knockout Nuclear Proteins/metabolism Sequence Deletion Trans-Activators/metabolism
Chemicals
Cyclic AMP Response Element-Binding Protein Nuclear Proteins Trans-Activators CREB-Binding Protein Crebbp protein, mouse E1A-Associated p300 Protein Ep300 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rebel Vivienne I
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Kung Andrew L
Tanner Elizabeth A
Yang Hong
Bronson Roderick T
Livingston David M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.232568499
Published
2002-11-12
Epub
2002-00-23
Pages
14789-94
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC137497
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.232568499 PMC Full Text View journal details
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