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Science 19 December 2003:
Vol. 302. no. 5653, pp. 2137 - 2140
DOI: 10.1126/science.1092481
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Reports

Transcription-Coupled Events Associating with Immunoglobulin Switch Region Chromatin

Yukiko Nambu,1* Manabu Sugai,1*{dagger} Hiroyuki Gonda,1,2 Chung-Gi Lee,3 Tomoya Katakai,1 Yasutoshi Agata,1{ddagger} Yoshifumi Yokota,4 Akira Shimizu1,2{dagger}

Class switch recombination (CSR) at the antibody immunoglobulin locus is regulated by germline transcription (GLT)–coupled modifications in the accessibility of the switch region, where CSR takes place. Here we show that histone acetylation of switch regions is linked to CSR but that histone acetylation cannot alone promote CSR or GLT. Activation-induced cytidine deaminase (AID) specifically associates with the CSR target chromatin in a GLT-coupled manner, which may occur potentially by means of physical interaction between AID and the transcription machinery. These data indicate an important role of GLT in the regulation of chromatin accessibility, strongly suggesting that the target of AID is chromatin DNA. Our results give insights on the role of AID and the regulatory mechanism of CSR.

1 Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
2 Translational Research Center, Kyoto University Hospital, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
3 Laboratory of Cellular Immunology, Alton Ochsner Medical Foundation, 1516 Jefferson Highway, New Orleans, LA 70121, USA.
4 Department of Biochemistry, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.



* These authors contributed equally to this work.

{ddagger} Present address: Horizontal Medical Research Organization, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.

{dagger} To whom correspondence should be addressed. E-mail: msugai{at}virus.kyoto-u.ac.jp (M.S.); shimizu{at}virus.kyoto-u.ac.jp (A.S.)

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