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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4407-4416. Prepublished online as a Blood First Edition Paper on January 19, 2006; DOI 10.1182/blood-2005-08-3263. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2005-08-3263v1 107/11/4407    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Xu, W. Articles by Brindle, P. K. Search for Related Content PubMed PubMed Citation Articles by Xu, W. Articles by Brindle, P. K. Related Collections Gene Expression Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells Wu Xu, Tomofusa Fukuyama, Paul A. Ney, Demin Wang, Jerold Rehg, Kelli Boyd, Jan M. A. van Deursen, and Paul K. Brindle From the Departments of Biochemistry and Pathology, St Jude Children's Research Hospital, Memphis, TN; Blood Research Institute, Blood Center of Wisconsin, Milwaukee; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee; and Departments of Pediatric and Adolescent Medicine and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN. 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 (p300flox), which carry CD19Cre that initiates floxed gene recombination at the pro–B-cell stage. CD19Cre-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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. I. Kuraishy, S. W. French, M. Sherman, M. Herling, D. Jones, R. Wall, and M. A. Teitell TORC2 regulates germinal center repression of the TCL1 oncoprotein to promote B cell development and inhibit transformation PNAS, June 12, 2007; 104(24): 10175 - 10180. [Abstract] [Full Text] [PDF] N. Forster, S. Gallinat, J. Jablonska, S. Weiss, H.-P. Elsasser, and W. Lutz p300 Protein Acetyltransferase Activity Suppresses Systemic Lupus Erythematosus-Like Autoimmune Disease in Mice J. Immunol., June 1, 2007; 178(11): 6941 - 6948. [Abstract] [Full Text] [PDF]

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