Progesterone inhibits activation-induced deaminase by binding to the promoter.

Abstract

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-kappaB 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.

• Authors: Siim Pauklin, Svend K Petersen-Mahrt
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 2 Pg. 1238-44 (Jul 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19553525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Progesterone
• AICDA (activation-induced cytidine deaminase)
• Cytidine Deaminase

Topics

• Animals
• B-Lymphocytes (immunology)
• Cytidine Deaminase (antagonists & inhibitors, genetics)
• Down-Regulation (drug effects)
• Female
• Immunoglobulin Class Switching
• Lymphocyte Activation
• Mice
• Mice, Inbred C57BL
• Progesterone (pharmacology)
• Promoter Regions, Genetic (drug effects)
• RNA, Messenger (biosynthesis)
• Somatic Hypermutation, Immunoglobulin
• Spleen (cytology)
• Transcription, Genetic (drug effects)