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Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells. Blood 2006 Jun 01;107(11):4407-16

Date

01/21/2006

Pubmed ID

16424387

Pubmed Central ID

PMC1895794

DOI

10.1182/blood-2005-08-3263

Scopus ID

2-s2.0-33744495991   41 Citations

Abstract

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 (CBP(flox)) 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.

Author List

Xu W, Fukuyama T, Ney PA, Wang D, Rehg J, Boyd K, van Deursen JM, Brindle PK

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alleles
Animals
Antigens, CD19
B-Lymphocytes
CREB-Binding Protein
Homeostasis
Integrases
Lymphocyte Count
Mice
p300-CBP Transcription Factors
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1