Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal.
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.
Rebel
Vivienne I
VI
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Kung
Andrew L
AL
Tanner
Elizabeth A
EA
Yang
Hong
H
Bronson
Roderick T
RT
Livingston
David M
DM
D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D050882:CREB-Binding Protein; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D003433:Crosses, Genetic; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein; D019337:Hematologic Neoplasms / Q000517:prevention & control; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse