Structure and Function of Histone H3 Lysine 9 Methyltransferases and Demethylases

被引：72

作者：

Krishnan, Swathi ^{[1
]}

Horowitz, Scott ^{[2
]}

Trievel, Raymond C. ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Biophys Grad Program, Ann Arbor, MI 48109 USA

来源：

CHEMBIOCHEM | 2011年 / 12卷 / 02期

关键词：

chromatin; demethylases; histone; methylation; transcription; transferases; LINKED MENTAL-RETARDATION; PERICENTRIC HETEROCHROMATIN; SUBSTRATE-SPECIFICITY; PRODUCT SPECIFICITY; DNA METHYLATION; JUMONJI DOMAIN; JMJD2; FAMILY; PHF8; GENE; G9A; PROTEIN;

D O I：

10.1002/cbic.201000545

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 lysine methylation is a dynamic chromatin modification that plays key regulatory roles in gene expression and other genomic functions. Methylation of Lys9 in histone H3 (H3K9) is a prominent modification that has been implicated in diverse processes, including transcriptional silencing, heterochromatin formation, and DNA methylation. In this review, we summarize recent advances in understanding the structure and substrate specificity of the H3K9-specific methyltransferases G9A and GLP and explore current efforts to develop inhibitors of these enzymes. In addition, we discuss the structure and specificity of the recently discovered PHF8 family of histone demethylases that target H3K9 as well as other methylation sites in histones H3 and H4. Finally, we conclude by comparing the H3K9 binding modes displayed by these enzymes and examine the relevance of these studies to their biological functions and to structure-based inhibitor design.

引用

页码：254 / 263

页数：10

共 104 条

[1] A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate [J].

Abidi, F. E. ;

Miano, M. G. ;

Murray, J. C. ;

Schwartz, C. E. .

CLINICAL GENETICS, 2007, 72 (01) :19-22

[2] The Universal Protein Resource (UniProt) in 2010 [J].

Apweiler, Rolf ;

Martin, Maria Jesus ;

O'Donovan, Claire ;

Magrane, Michele ;

Alam-Faruque, Yasmin ;

Antunes, Ricardo ;

Barrell, Daniel ;

Bely, Benoit ;

Bingley, Mark ;

Binns, David ;

Bower, Lawrence ;

Browne, Paul ;

Chan, Wei Mun ;

Dimmer, Emily ;

Eberhardt, Ruth ;

Fedotov, Alexander ;

Foulger, Rebecca ;

Garavelli, John ;

Huntley, Rachael ;

Jacobsen, Julius ;

Kleen, Michael ;

Laiho, Kati ;

Leinonen, Rasko ;

Legge, Duncan ;

Lin, Quan ;

Liu, Wudong ;

Luo, Jie ;

Orchard, Sandra ;

Patient, Samuel ;

Poggioli, Diego ;

Pruess, Manuela ;

Corbett, Matt ;

di Martino, Giuseppe ;

Donnelly, Mike ;

van Rensburg, Pieter ;

Bairoch, Amos ;

Bougueleret, Lydie ;

Xenarios, Ioannis ;

Altairac, Severine ;

Auchincloss, Andrea ;

Argoud-Puy, Ghislaine ;

Axelsen, Kristian ;

Baratin, Delphine ;

Blatter, Marie-Claude ;

Boeckmann, Brigitte ;

Bolleman, Jerven ;

Bollondi, Laurent ;

Boutet, Emmanuel ;

Quintaje, Silvia Braconi ;

Breuza, Lionel .

NUCLEIC ACIDS RESEARCH, 2010, 38 :D142-D148

[3] High-resolution profiling of histone methylations in the human genome [J].

Barski, Artern ;

Cuddapah, Suresh ;

Cui, Kairong ;

Roh, Tae-Young ;

Schones, Dustin E. ;

Wang, Zhibin ;

Wei, Gang ;

Chepelev, Iouri ;

Zhao, Keji .

CELL, 2007, 129 (04) :823-837

[4] The complex language of chromatin regulation during transcription [J].

Berger, Shelley L. .

NATURE, 2007, 447 (7143) :407-412

[5] Covalent modifications of histones during development and disease pathogenesis [J].

Bhaumik, Sukesh R. ;

Smith, Edwin ;

Shilatifard, Ali .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (11) :1008-1016

[6] Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes [J].

Boggs, BA ;

Cheung, P ;

Heard, E ;

Spector, DL ;

Chinault, AC ;

Allis, CD .

NATURE GENETICS, 2002, 30 (01) :73-76

[7] Adding a Lysine Mimic in the Design of Potent Inhibitors of Histone Lysine Methyltransferases [J].

Chang, Yanqi ;

Ganesh, Thota ;

Horton, John R. ;

Spannhoff, Astrid ;

Liu, Jin ;

Sun, Aiming ;

Zhang, Xing ;

Bedford, Mark T. ;

Shinkai, Yoichi ;

Snyder, James P. ;

Cheng, Xiaodong .

JOURNAL OF MOLECULAR BIOLOGY, 2010, 400 (01) :1-7

[8] Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294 [J].

Chang, Yanqi ;

Zhang, Xing ;

Horton, John R. ;

Upadhyay, Anup K. ;

Spannhoff, Astrid ;

Liu, Jin ;

Snyder, James P. ;

Bedford, Mark T. ;

Cheng, Xiaodong .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2009, 16 (03) :312-317

[9] Structural insights into histone demethylation by JMJD2 family members [J].

Chen, Zhongzhou ;

Zang, Jianye ;

Whetstine, Johnathan ;

Hong, Xia ;

Davrazou, Foteini ;

Kutateladze, Tatiana G. ;

Simpson, Michael ;

Mao, Qilong ;

Pan, Cheol-Ho ;

Dai, Shaodong ;

Hagman, James ;

Hansen, Kirk ;

Shi, Yang ;

Zhang, Gongyi .

CELL, 2006, 125 (04) :691-702

[10] Structural basis of the recognition of a methylated histone tail by JMJD2A [J].

Chen, Zhongzhou ;

Zang, Jianye ;

Kappler, John ;

Hong, Xia ;

Crawford, Frances ;

Wang, Qin ;

Lan, Fei ;

Jiang, Chengyu ;

Whetstine, Johnathan ;

Dai, Shaodong ;

Hansen, Kirk ;

Shi, Yang ;

Zhang, Gongyi .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (26) :10818-10823

← 1 2 3 4 5 6 7 8 9 10 →