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

Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14789-94. doi: 10.1073/pnas.232568499. Epub 2002 Oct 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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
  • Cyclic AMP Response Element-Binding Protein / 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*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Nuclear Proteins
  • Trans-Activators
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse