title: GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells.
abstract: GCN5 is involved in the acetylation of core histones, which is an important epigenetic event for transcriptional regulation through alterations in the chromatin structure in eukaryotes. To investigate physiological roles of GCN5, we have systematically analyzed phenotypes of homozygous GCN5-deficient DT40 mutants. Here, we report participation of GCN5 in regulation of IgM heavy chain (H-chain) gene expression. GCN5-deficiency down-regulates gene expressions of IgM H-chain (as whole, membrane-bound and secreted forms of its mRNA) but not light chain (L-chain), causing decreases in membrane-bound and secreted forms of IgM proteins. Chromatin immnoprecipitation assay revealed that GCN5 binds to the chicken IgM H-chain gene around its constant region but not L-chain gene, and acetylate Lys-9 residues of histone H3 within chromatin surrounding the constant region. These results suggest that GCN5 takes part in transcriptional regulation of the IgM H-chain gene via histone acetylation resulting in formation of relaxed chromatin arrangement around its coding region and plays a key role in epigenetic regulation of B cell functions.
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan; Laboratory Center for Proteomics Research, Graduate School of Frontier Sciences, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan. Electronic address: masakari@med.miyazaki-u.ac.jp.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Laboratory Center for Proteomics Research, Graduate School of Frontier Sciences, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan; Department of Biochemistry, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Kuribayashi
authors.affiliation: Laboratory Center for Proteomics Research, Graduate School of Frontier Sciences, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishitoh
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Takami
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000107:Acetylation; D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002645:Chickens; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D015151:Immunoblotting; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D030161:Avian Proteins; D002843:Chromatin; D006657:Histones; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D008565:Membrane Proteins; D051548:Histone Acetyltransferases; D008239:Lysine
keywords: DT40; GCN5; Gene targeting; Histone acetyltransferase; Immunoglobulin