期刊
BLOOD
卷 107, 期 11, 页码 4407-4416出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-08-3263
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资金
- NCI NIH HHS [P30 CA021765-28, R01 CA076385] Funding Source: Medline
- NHLBI NIH HHS [R01 HL073284] Funding Source: Medline
- NIDDK NIH HHS [R01 DK053469-03, R01 DK053469-04, R01 DK053469-02, R01 DK053469-01A2] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA076385, P30CA021765] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL073284] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK053469] Funding Source: NIH RePORTER
CREB-binding protein (CBP) and its para-log p300 are transcriptional coactivators that physically or functionally interact with over 320 mammalian and viral proteins, including 36 that are essential for B cells in mice. CBP and p300 are generally considered limiting for transcription, yet their roles in adult cell lineages are largely unknown since homozygous null mutations in either gene or compound heterozygosity cause early embryonic lethality in mice. We tested the hypotheses that CBP and p300 are limiting and that each has unique properties in B cells, by using mice with Cre/LoxP conditional knockout alleles for CBP (CBPflox) and p300 (p300(flox)), which carry CD19(Cre) that initiates floxed gene recombination at the pro-B-cell stage. CD19(Cre)-mediated loss of CBP or p300 led to surprisingly modest deficits in B-cell numbers, whereas inactivation of both genes was not tolerated by peripheral B cells. There was a moderate decrease in B-cell receptor (BCR)-responsive gene expression in CBP or p300 homozygous null B cells, suggesting that CBP and p300 are essential for this signaling pathway that is crucial for B-cell homeostasis. These results indicate that individually CBP and p300 are partially limiting beyond the pro-B-cell stage and that other coactivators in B cells cannot replace their combined loss.
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