Histone acetyltransferase PCAF is involved in transactivation of Bcl-6 and Pax5 genes in immature B cells

被引:2
|
作者
Kikuchi, Hidehiko [1 ,2 ]
Nakayama, Masami [1 ]
Kuribayashi, Futoshi [2 ,3 ]
Mimuro, Hitomi [2 ]
Imajoh-Ohmi, Shinobu [4 ]
Nishitoh, Hideki [1 ]
Nakayama, Tatsuo [1 ]
机构
[1] Miyazaki Univ, Fac Med, Dept Med Sci, Sect Biochem & Mol Biol, Kiyotake, Miyazaki 8891692, Japan
[2] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Div Bacteriol,Dept Infect Dis Control,Minato Ku, Tokyo 1088639, Japan
[3] Kawasaki Med Sch, Dept Biochem, Kurashiki, Okayama 7010192, Japan
[4] Univ Tokyo, Inst Med Sci, Grad Sch Frontier Sci, Lab Ctr Prote Res,Minato Ku, Tokyo 1088639, Japan
关键词
B cell development; DT40; Epigenetics; Gene targeting; Histone acetyltransferase; TRANSCRIPTION FACTOR; P300/CBP-ASSOCIATED FACTOR; DIFFERENTIATION; PROTEIN; CHAIN; GCN5; E2A; COACTIVATORS; ACTIVATION; EXPRESSION;
D O I
10.1016/j.bbrc.2015.10.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, Delta PCAF, 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. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:509 / 513
页数:5
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