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Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12620-3. Epub 2001 Oct 16.

A hallmark of active class switch recombination: transcripts directed by I promoters on looped-out circular DNAs.

Kinoshita K, Harigai M, Fagarasan S, Muramatsu M, Honjo T.

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Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-Ku, Kyoto 606-8501, Japan.

Abstract

To specify when and where Ig class switch recombination (CSR) takes place, a good molecular marker closely associated with active CSR is required. CSR is accompanied by deletion of circular DNA from the Ig heavy chain locus. The circular DNA contains a DNA segment between Smu and a target S region including its I promoter, which is driven by specific cytokine stimulation before CSR. We found that the specific I promoter is still active in looped-out circular DNA and directs production of I-Cmu transcripts termed "circle transcripts." Reverse transcription-PCR demonstrated transient induction of specific circle transcripts upon CSR in a murine lymphoma cell line, CH12F3-2A, as well as spleen B cells. Production of the circle transcripts appeared to depend on expression of activation-induced cytidine deaminase (AID), an essential factor for CSR. A comparison of kinetics between circle transcripts and circular DNA showed more rapid disappearance of circle transcripts. Thus, circle transcripts may serve as a hallmark for active CSR in vitro and in vivo.

PMID:: 11606740; [PubMed - indexed for MEDLINE]
PMCID:: PMC60103

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