title: Histone acetyltransferase PCAF is involved in transactivation of Bcl-6 and Pax5 genes in immature B cells.
abstract: Histone acetyltransferase p300/CBP-associated factor (PCAF) belonging to GCN5 family regulates various epigenetic events for transcriptional regulation through alterations in the chromatin structure. During normal development of B cells, gene expressions of numerous transcription factors are strictly regulated by epigenetic mechanisms including histone acetylation and deacetylation to complete their development pathways. Here, by analyzing PCAF-deficient DT40 mutants, ΔPCAF, we report that PCAF takes part in transcriptional activation of B cell lymphoma-6 (Bcl-6) and Paired box gene 5 (Pax5), which are essential transcription factors for normal development of B cells. PCAF-deficiency caused drastic decrease in mRNA levels of Bcl-6 and Pax5, and remarkable increase in that of B lymphocyte-induced maturation protein-1 (Blimp-1). In addition, chromatin immunoprecipitation assay showed that PCAF-deficiency caused remarkable decrease in acetylation levels of both H3K9 and H3K14 residues within chromatin surrounding the 5'-flanking regions of Bcl-6 and Pax5 genes in vivo, suggesting that their gene expressions may be regulated by PCAF. These results revealed that PCAF is involved in transactivation of Bcl-6 and Pax5 genes, resulting in down-regulation of Blimp-1 gene expression, and plays a key role in epigenetic regulation of B cell development.
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; Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 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: Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 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: Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mimuro
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, Minato-ku, 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: Tatsuo
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D051757:PAX5 Transcription Factor / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D051757:PAX5 Transcription Factor; D051560:Proto-Oncogene Proteins c-bcl-6; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
keywords: B cell development; DT40; Epigenetics; Gene targeting; Histone acetyltransferase