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¹ Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612
² Université Paul Sabatier, III, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5089–Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse Cedex, France

CORRESPONDENCE Amy L. Kenter: star1{at}uic.edu

Immunoglobulin class switch recombination is governed by long-range interactions between enhancers and germline transcript promoters to activate transcription and modulate chromatin accessibility to activation-induced cytidine deaminase (AID). However, mechanisms leading to the differential targeting of AID to switch (S) regions but not to constant (C_H) regions remain unclear. We show that S and C_H regions are dynamically modified with histone marks that are associated with active and repressed chromatin states, respectively. Chromatin accessibility is superimposable with the activating histone modifications, which extend throughout S regions irrespective of length. High density elongating RNA polymerase II (RNAP II) is detected in S regions, suggesting that the transcription machinery has paused and stalling is abolished by deletion of the S region. We propose that RNAP II enrichment facilitates recruitment of histone modifiers to generate accessibility. Thus, the histone methylation pattern produced by transcription localizes accessible chromatin to S regions, thereby focusing AID attack.

Abbreviations used: Ac, acetylation; AID, activation-induced cytidine deaminase; C_H, constant; ChIP, chromatin immunoprecipitation; CSR, class switch recombination; DC-PCR, digestion circularization PCR; DSB, double-strand break; GLT, germline transcript; H3Ac, acetylated histone H3K9,K14; HAT, histone acetyltransferase; HDAC, histone deacetylase; HMT, histone methyltransferase; Me, methylation; PST, postswitch transcript; qPCR, quantitative real-time PCR; qRT-PCR, quantitative real-time RT-PCR; RES, restriction sensitivity endonuclease; RNAP II, RNA polymerase II; S, switch; TSA, trichostatin A; TSS, transcription start site.

© 2009 Wang et al.
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This article has been cited by other articles:

• Wang, L., Wuerffel, R., Feldman, S., Khamlichi, A. A., Kenter, A. L. (2009). S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination. JCB 186: i4-i4 [Full Text]  

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