Transcription-coupled events associating with immunoglobulin switch region chromatin.
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.
Nambu
Yukiko
Y
Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Sugai
Manabu
M
Gonda
Hiroyuki
H
Lee
Chung-Gi
CG
Katakai
Tomoya
T
Agata
Yasutoshi
Y
Yokota
Yoshifumi
Y
Shimizu
Akira
A
D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007134:Immunoglobulin Switch Region; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D011233:Precipitin Tests; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology; D053773:Transforming Growth Factor beta1; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007073:Immunoglobulin E; C012589:trichostatin A; D012313:RNA; D004247:DNA; D012319:RNA Polymerase II; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase