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

JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications

(2021) Vignesh Kasinath et al.   SCIENCE

Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome

(2020) Evan J Worden et al.   eLife

Small Molecule Approaches for Targeting the Polycomb Repressive Complex 2 (PRC2) in Cancer

(2020) M. Cynthia Martin et al.   JOURNAL OF MEDICINAL CHEMISTRY

‘It will change everything’: DeepMind’s AI makes gigantic leap in solving protein structures

(2020) Ewen Callaway   NATURE

Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases

(2020) Wanqiu Li et al.   NATURE

Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3

(2020) Ksenia Finogenova et al.   eLife

Structural Basis of MRG15-Mediated Activation of the ASH1L Histone Methyltransferase by Releasing an Autoinhibitory Loop

(2019) Yoonjung Lee et al.   STRUCTURE

Structural Insights into Stimulation of Ash1L's H3K36 Methyltransferase Activity through Mrg15 Binding

(2019) Peini Hou et al.   STRUCTURE

RNA exploits an exposed regulatory site to inhibit the enzymatic activity of PRC2

(2019) Qi Zhang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Allosteric Modulator Discovery: From Serendipity to Structure-Based Design

(2019) Shaoyong Lu et al.   JOURNAL OF MEDICINAL CHEMISTRY

PRC2 is high maintenance

(2019) Jia-Ray Yu et al.   GENES & DEVELOPMENT

Why are so many MLL lysine methyltransferases required for normal mammalian development?

(2019) Nicholas T. Crump et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

EED inhibition suppresses cancers by modulating the immune response

(2019) Hongping Dong et al.   CANCER RESEARCH

PRC2 functions in development and congenital disorders

(2019) Orla Deevy et al.   DEVELOPMENT

Structural basis of nucleosome recognition and modification by MLL methyltransferases

(2019) Han Xue et al.   NATURE

Targeting epigenetic machinery: Emerging novel allosteric inhibitors

(2019) Fei Ye et al.   PHARMACOLOGY & THERAPEUTICS

The Complexity of PRC2 Subcomplexes

(2019) Guido van Mierlo et al.   TRENDS IN CELL BIOLOGY

Engaging chromatin: PRC2 structure meets function

(2019) Paul Chammas et al.   BRITISH JOURNAL OF CANCER

Histone lysine methyltransferases in biology and disease

(2019) Dylan Husmann et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Nucleosome and ubiquitin position Set2 to methylate H3K36

(2019) Silvija Bilokapic et al.   Nature Communications

Structural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS

(2019) Peter L. Hsu et al.   MOLECULAR CELL

Cryo-EM structure of the human MLL1 core complex bound to the nucleosome

(2019) Sang Ho Park et al.   Nature Communications

Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC

(2018) Sigrun Schmähling et al.   DEVELOPMENT

Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin

(2018) Chul-Hwan Lee et al.   MOLECULAR CELL

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR / LCORL Genes Balance PRC2 Subtype Activities

(2018) Eric Conway et al.   MOLECULAR CELL

Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes

(2018) Simon Poepsel et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structures of human PRC2 with its cofactors AEBP2 and JARID2

(2018) Vignesh Kasinath et al.   SCIENCE

Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes

(2018) Simon Poepsel et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module

(2018) Peter L. Hsu et al.   CELL

Structure and Conformational Dynamics of a COMPASS Histone H3K4 Methyltransferase Complex

(2018) Qianhui Qu et al.   CELL

Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability

(2018) Nahid Iglesias et al.   NATURE

Polycomb repressive complex 2 in an autoinhibited state

(2017) Matthew Bratkowski et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy

(2017) Ying Huang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines

(2017) Xueyin Wang et al.   MOLECULAR CELL

An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED

(2017) Wei Qi et al.   Nature Chemical Biology

The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex

(2017) Yupeng He et al.   Nature Chemical Biology

Allosteric histone methyltransferase modulators block tumour growth

(2017) Sarah Crunkhorn   NATURE REVIEWS DRUG DISCOVERY

Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila

(2017) Chang Huang et al.   Nature Communications

Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2

(2017) Yicheng Long et al.   eLife

MLL-Rearranged Leukemias—An Update on Science and Clinical Approaches

(2017) Amanda C. Winters et al.   Frontiers in Pediatrics

Nucleosome Binding Alters the Substrate Bonding Environment of Histone H3 Lysine 36 Methyltransferase NSD2

(2016) Myles B. Poulin et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Structural basis for activity regulation of MLL family methyltransferases

(2016) Yanjing Li et al.   NATURE

A two-state activation mechanism controls the histone methyltransferase Suv39h1

(2016) Manuel M Müller et al.   Nature Chemical Biology

The molecular hallmarks of epigenetic control

(2016) C. David Allis et al.   NATURE REVIEWS GENETICS

Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2

(2016) Neil Justin et al.   Nature Communications

Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins

(2016) Lianhua Piao et al.   Oncotarget

A High-Density Map for Navigating the Human Polycomb Complexome

(2016) Simon Hauri et al.   Cell Reports

Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

(2016) Ludovica Morera et al.   Clinical Epigenetics

Unique Role of the WD-40 Repeat Protein 5 (WDR5) Subunit within the Mixed Lineage Leukemia 3 (MLL3) Histone Methyltransferase Complex

(2015) Stephen A. Shinsky et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Toward a Consensus on the Binding Specificity and Promiscuity of PRC2 for RNA

(2015) Chen Davidovich et al.   MOLECULAR CELL

Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation

(2015) Serena Sanulli et al.   MOLECULAR CELL

Sound of silence: the properties and functions of repressive Lys methyltransferases

(2015) Chiara Mozzetta et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2

(2015) Chen Davidovich et al.   RNA

Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2

(2015) L. Jiao et al.   SCIENCE

Evolving Catalytic Properties of the MLL Family SET Domain

(2015) Ying Zhang et al.   STRUCTURE

Constitutive heterochromatin formation and transcription in mammals

(2015) Nehmé Saksouk et al.   Epigenetics & Chromatin

Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer

(2015) Huiming Chen et al.   Oncotarget

Astemizole Arrests the Proliferation of Cancer Cells by Disrupting the EZH2-EED Interaction of Polycomb Repressive Complex 2

(2014) Xiangqian Kong et al.   JOURNAL OF MEDICINAL CHEMISTRY

A dimeric state for PRC2

(2014) Chen Davidovich et al.   NUCLEIC ACIDS RESEARCH

The trithorax group proteins Kismet and ASH1 promote H3K36 dimethylation to counteract Polycomb group repression in Drosophila

(2013) K. M. Dorighi et al.   DEVELOPMENT

Occupying Chromatin: Polycomb Mechanisms for Getting to Genomic Targets, Stopping Transcriptional Traffic, and Staying Put

(2013) Jeffrey A. Simon et al.   MOLECULAR CELL

Division of Labor between the Chromodomains of HP1 and Suv39 Methylase Enables Coordination of Heterochromatin Spread

(2013) Bassem Al-Sady et al.   MOLECULAR CELL

ASH2L Regulates Ubiquitylation Signaling to MLL: trans-Regulation of H3 K4 Methylation in Higher Eukaryotes

(2013) Lipeng Wu et al.   MOLECULAR CELL

Histone Crosstalk: H2Bub and H3K4 Methylation

(2013) Luis M. Soares et al.   MOLECULAR CELL

Targeted disruption of the EZH2–EED complex inhibits EZH2-dependent cancer

(2013) Woojin Kim et al.   Nature Chemical Biology

Promiscuous RNA binding by Polycomb repressive complex 2

(2013) Chen Davidovich et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structure of the Catalytic Domain of EZH2 Reveals Conformational Plasticity in Cofactor and Substrate Binding Sites and Explains Oncogenic Mutations

(2013) Hong Wu et al.   PLoS One

Structural Context of Disease-Associated Mutations and Putative Mechanism of Autoinhibition Revealed by X-Ray Crystallographic Analysis of the EZH2-SET Domain

(2013) Stephen Antonysamy et al.   PLoS One

Small molecule epigenetic inhibitors targeted to histone lysine methyltransferases and demethylases

(2013) Zhanxin Wang et al.   QUARTERLY REVIEWS OF BIOPHYSICS

Noncoding RNA and Polycomb recruitment

(2013) N. Brockdorff   RNA

Ash1l Methylates Lys36 of Histone H3 Independently of Transcriptional Elongation to Counteract Polycomb Silencing

(2013) Hitomi Miyazaki et al.   PLoS Genetics

H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation

(2013) Ji-Eun Lee et al.   eLife

The COMPASS Family of Histone H3K4 Methylases: Mechanisms of Regulation in Development and Disease Pathogenesis

(2012) Ali Shilatifard   Annual Review of Biochemistry

Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2

(2012) Weihong Zheng et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Polycomb Repressive Complex 2-Dependent and -Independent Functions of Jarid2 in Transcriptional Regulation in Drosophila

(2012) H.-M. Herz et al.   MOLECULAR AND CELLULAR BIOLOGY

Histone Lysine Methylation Dynamics: Establishment, Regulation, and Biological Impact

(2012) Joshua C. Black et al.   MOLECULAR CELL

Chromatin as an expansive canvas for chemical biology

(2012) Beat Fierz et al.   Nature Chemical Biology

Understanding the language of Lys36 methylation at histone H3

(2012) Eric J. Wagner et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Crystal Structure of the Human SUV39H1 Chromodomain and Its Recognition of Histone H3K9me2/3

(2012) Tao Wang et al.   PLoS One

Regulation of chromatin by histone modifications

(2011) Andrew J Bannister et al.   CELL RESEARCH

The Structure of NSD1 Reveals an Autoregulatory Mechanism Underlying Histone H3K36 Methylation

(2011) Qi Qiao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Crystal Structure of the Human Histone Methyltransferase ASH1L Catalytic Domain and Its Implications for the Regulatory Mechanism

(2011) Sojin An et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

H3K36 Methylation Antagonizes PRC2-mediated H3K27 Methylation

(2011) Wen Yuan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks

(2011) Frank W. Schmitges et al.   MOLECULAR CELL

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human

(2011) Y.-h. Takahashi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Histone lysine methylation and demethylation pathways in cancer

(2010) Radhika A. Varier et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome

(2010) Sarah B Ng et al.   NATURE GENETICS

Structural Biology of Human H3K9 Methyltransferases

(2010) Hong Wu et al.   PLoS One

Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2)

(2010) C. Xu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Therapeutic targeting of MLL

(2009) M. Liedtke et al.   BLOOD

The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate

(2009) Yan Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structural Basis for the Requirement of Additional Factors for MLL1 SET Domain Activity and Recognition of Epigenetic Marks

(2009) Stacey M. Southall et al.   MOLECULAR CELL

Role of the polycomb protein EED in the propagation of repressive histone marks

(2009) Raphael Margueron et al.   NATURE

Histone methyltransferases in cancer

(2009) Mareike Albert et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

A model for transmission of the H3K27me3 epigenetic mark

(2008) Klaus H. Hansen et al.   NATURE CELL BIOLOGY

Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin

(2008) Ke Zhang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Allostery and cooperativity revisited

(2008) Qiang Cui et al.   PROTEIN SCIENCE

Allostery: an illustrated definition for the ‘second secret of life’

(2008) Aron W. Fenton   TRENDS IN BIOCHEMICAL SCIENCES