Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal
VI Rebel, AL Kung, EA Tanner, H Yang… - Proceedings of the …, 2002 - pnas.org
VI Rebel, AL Kung, EA Tanner, H Yang, RT Bronson, DM Livingston
Proceedings of the National Academy of Sciences, 2002•pnas.orgHematopoietic 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 …
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 …
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.
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