title: Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal.
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.
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Vivienne I
authors.initials: VI
authors.lastname: Rebel
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kung
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Tanner
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: David M
authors.initials: DM
authors.lastname: Livingston
mesh_terms: 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*
chemical_list: 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