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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0803915v1 183/2/1238    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Pauklin, S. Articles by Petersen-Mahrt, S. K. PubMed PubMed Citation Articles by Pauklin, S. Articles by Petersen-Mahrt, S. K.

Progesterone Inhibits Activation-Induced Deaminase by Binding to the Promoter¹

DNA Editing Lab, Clare Hall Laboratories, Cancer Research U.K., South Mimms, United Kingdom

Regulation of activation-induced deaminase (AID), an essential factor in Ig diversification, can alter not only somatic hypermutation and class switch recombination (CSR), but may also influence oncogenesis. AID deaminates cytosine to uracil in the Ig locus, thereby initiating Ig diversification. Unregulated AID can induce oncogenic DNA alterations in Ig and non-Ig loci, leading to mutations, recombination, and translocations. In this study, we demonstrate that AID mRNA production in activated mouse splenic B cells can be reduced by treatment with the sex hormone progesterone. This down-regulation is independent of translation or splicing and is predominantly achieved by inhibiting transcription. During cell treatment we could detect progesterone receptor bound to the AID promoter in proximity to NF-B binding. Importantly, the progesterone-induced repression was also extended to the protein level of AID and its activity on somatic hypermutation and class switch recombination.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by SA Archimedes, Estonian Foundation of European Union Education and Research, and Cancer Research UK.

² Address correspondence and reprint requests to Dr. Svend K. Petersen-Mahrt, Clare Hall Laboratories, London Research Institute, Cancer Research U.K., South Mimms EN6 3LD, U.K. E-mail address: skpm{at}cancer.org.uk

³ Abbreviations used in this paper: SHM, somatic hypermutation; AID, activation-induced deaminase; CSR, class switch recombination; PR, progesterone receptor; ChIP, chromatin immunoprecipitation; ERE, estrogen response element; PRE, progesterone response element.

⁴ The online version of this article contains supplemental material.