Allosteric regulation of histone lysine methyltransferases: From context-specific regulation to selective drugs

Chen Davidovich; Qi Zhang

doi:10.1042/BST20200238

Allosteric regulation of histone lysine methyltransferases: From context-specific regulation to selective drugs

Chen Davidovich, Qi Zhang

Research output: Contribution to journal › Review Article › Research › peer-review

6 Citations (Scopus)

Abstract

Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, with their allosteric regulation emerging as a prevalent paradigm. We review the molecular mechanisms of allosteric regulation of HKMTs using well-studied histone H3 (K4, K9, K27 and K36) methyltransferases as examples. We discuss the current advances and future potential in targeting allosteric sites of HKMTs for drug development.

Original language	English
Pages (from-to)	591-607
Number of pages	17
Journal	Biochemical Society Transactions
Volume	49
Issue number	2
DOIs	https://doi.org/10.1042/BST20200238
Publication status	Published - Apr 2021

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10.1042/BST20200238Licence: CC BY

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title = "Allosteric regulation of histone lysine methyltransferases: From context-specific regulation to selective drugs",

abstract = "Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, with their allosteric regulation emerging as a prevalent paradigm. We review the molecular mechanisms of allosteric regulation of HKMTs using well-studied histone H3 (K4, K9, K27 and K36) methyltransferases as examples. We discuss the current advances and future potential in targeting allosteric sites of HKMTs for drug development.",

author = "Chen Davidovich and Qi Zhang",

note = "Funding Information: Q.Z. was supported by Australian Research Council (ARC), Discovery Early Career Researcher Award (DE180100219), and National Health and Medical Research Council (NHMRC) Investigator grant (APP1196365). C.D. is an EMBL-Australia Group Leader and a Sylvia and Charles Viertel Senior Medical Research Fellow, and acknowledges support from the ARC (DP190103407) and the NHMRC (APP1162921 \& APP1184637). Publisher Copyright: {\textcopyright} 2021 Portland Press Ltd. All rights reserved.",

year = "2021",

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doi = "10.1042/BST20200238",

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T1 - Allosteric regulation of histone lysine methyltransferases

T2 - From context-specific regulation to selective drugs

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AU - Zhang, Qi

N1 - Funding Information: Q.Z. was supported by Australian Research Council (ARC), Discovery Early Career Researcher Award (DE180100219), and National Health and Medical Research Council (NHMRC) Investigator grant (APP1196365). C.D. is an EMBL-Australia Group Leader and a Sylvia and Charles Viertel Senior Medical Research Fellow, and acknowledges support from the ARC (DP190103407) and the NHMRC (APP1162921 & APP1184637). Publisher Copyright: © 2021 Portland Press Ltd. All rights reserved.

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N2 - Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, with their allosteric regulation emerging as a prevalent paradigm. We review the molecular mechanisms of allosteric regulation of HKMTs using well-studied histone H3 (K4, K9, K27 and K36) methyltransferases as examples. We discuss the current advances and future potential in targeting allosteric sites of HKMTs for drug development.

AB - Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, with their allosteric regulation emerging as a prevalent paradigm. We review the molecular mechanisms of allosteric regulation of HKMTs using well-studied histone H3 (K4, K9, K27 and K36) methyltransferases as examples. We discuss the current advances and future potential in targeting allosteric sites of HKMTs for drug development.

UR - https://www.scopus.com/pages/publications/85105642489

U2 - 10.1042/BST20200238

DO - 10.1042/BST20200238

M3 - Review Article

C2 - 33769454

AN - SCOPUS:85105642489

SN - 0300-5127

VL - 49

SP - 591

EP - 607

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

IS - 2

ER -

Allosteric regulation of histone lysine methyltransferases: From context-specific regulation to selective drugs

Abstract

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Molecular mechanism for the regulation of Polycomb repressive complex 2

RNA-mediated regulation of the histone methyltransferase PRC2: a new link to disease-associated and causing mutations

Crosstalk between the repressive histone methyltransferases PRC2 and G9A: structure-function investigation to open new therapeutic opportunities

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Allosteric regulation of histone lysine methyltransferases: From context-specific regulation to selective drugs

Abstract

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Projects

Molecular mechanism for the regulation of Polycomb repressive complex 2

RNA-mediated regulation of the histone methyltransferase PRC2: a new link to disease-associated and causing mutations

Crosstalk between the repressive histone methyltransferases PRC2 and G9A: structure-function investigation to open new therapeutic opportunities

Cite this