Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

被引:180
作者
Nakagawa, Takeya [1 ]
Kajitani, Takuya [1 ]
Togo, Shinji [2 ]
Masuko, Norio [3 ]
Ohdan, Hideki [4 ]
Hishikawa, Yoshitaka [1 ]
Koji, Takehiko [1 ]
Matsuyama, Toshifumi [1 ]
Ikura, Tsuyoshi [5 ]
Muramatsu, Masami [6 ]
Ito, Takashi [1 ]
机构
[1] Nagasaki Univ, Sch Med, Nagasaki 8528523, Japan
[2] Yokohama City Univ, Sch Med, Dept Surg 2, Yokohama, Kanagawa 2360004, Japan
[3] Taisho Pharmaceut Co Ltd, Hanno Res Ctr, Saitama 3578527, Japan
[4] Hiroshima Univ, Sch Med, Dept Surg, Hiroshima 7348553, Japan
[5] Tohoku Univ, Sch Med, Dept Biochem, Sendai, Miyagi 9808575, Japan
[6] Saitama Med Sch, Res Ctr Genom Med, Saitama 3501241, Japan
关键词
nucleosome; ubiquitylation; histone code; transcription; USP21; H2A;
D O I
10.1101/gad.1609708
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di- and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation.
引用
收藏
页码:37 / 49
页数:13
相关论文
共 55 条
  • [41] Raju J, 2003, CANCER RES, V63, P6595
  • [42] Methylation of histone H3K4 mediates association of the Isw1p ATPase with chromatin
    Santos-Rosa, H
    Schneider, R
    Bernstein, BE
    Karabetsou, N
    Morillon, A
    Weise, C
    Schreiber, SL
    Mellor, J
    Kouzarides, T
    [J]. MOLECULAR CELL, 2003, 12 (05) : 1325 - 1332
  • [43] Chromatin modifications by methylation and ubiquitination: Implications in the regulation of gene expression
    Shilatifard, Ali
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 : 243 - 269
  • [44] Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains
    Sims, RJ
    Chen, CF
    Santos-Rosa, H
    Kouzarides, T
    Patel, SS
    Reinberg, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (51) : 41789 - 41792
  • [45] The language of covalent histone modifications
    Strahl, BD
    Allis, CD
    [J]. NATURE, 2000, 403 (6765) : 41 - 45
  • [46] Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast
    Sun, ZW
    Allis, CD
    [J]. NATURE, 2002, 418 (6893) : 104 - 108
  • [47] G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis
    Tachibana, M
    Sugimoto, K
    Nozaki, M
    Ueda, J
    Ohta, T
    Ohki, M
    Fukuda, M
    Takeda, N
    Niida, H
    Kato, H
    Shinkai, Y
    [J]. GENES & DEVELOPMENT, 2002, 16 (14) : 1779 - 1791
  • [48] Rapid fabrication of microfluidic devices in poly(dimethylsiloxane) by photocopying
    Tan, AM
    Rodgers, K
    Murrihy, JP
    O'Mathuna, C
    Glennon, JD
    [J]. LAB ON A CHIP, 2001, 1 (01): : 7 - 9
  • [49] Liver regeneration .4. Transcriptional control of liver regeneration
    Taub, R
    [J]. FASEB JOURNAL, 1996, 10 (04) : 413 - 427
  • [50] Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray
    Togo, S
    Makino, H
    Kobayashi, T
    Morita, T
    Shimizu, T
    Kubota, T
    Ichikawa, Y
    Ishikawa, T
    Okazaki, Y
    Hayashizaki, Y
    Shimada, H
    [J]. JOURNAL OF HEPATOLOGY, 2004, 40 (03) : 464 - 471