crystal structure of the compass h3k4 methyltransferase

Crystal Structure of the COMPASS H3K4

2018-10-5Article Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module Peter L Hsu 1 Heng Li 1 Ho-Tak Lau 1 Calvin Leonen 2 Abhinav Dhall 2 Shao-En Ong 1 Champak Chatterjee 2 and Ning Zheng1 3 4 * 1Department of Pharmacology University of Washington Seattle WA 98195 USA 2Department of Chemistry University of Washington Seattle WA 98195 USA 3Howard Hughes

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INTRODUCTION Histone H3 K4 methylation (H3K4) is a post-translational modification (PTM) deposited by an evolutionary conserved family of lysine methyltransferases referred to as the l ysine M ethyl-T ransferase 2 (KMT2) () Also referred to as COMPlex Associated to SET1 (COMPASS) six human KMT2 enzymes contribute to different extent to the deposition of this PTM

Structural implications of Dpy30 oligomerization for

Crystal structure of human Fanconi-associated nuclease 1 Crystal structure of human Fanconi-associated nuclease 1 See also Structural implications of Dpy30 oligomerization for MLL/SET1 COMPASS H3K4 trimethylation Protein Cell Dec 2014 Hongmei Zhang Mei Li Yu Gao

Histone trimethylation by Set1 is coordinated by the

G990E replacement in Set1 creates a hyperactive H3K4 methyltransferase (A) Structure of the Set7/9 SET domain (Xiao et al 2003) The G990E dominant mutation in Set1 corresponds to G264 of Set7/9 (pink) (B) Purification of WT and G990E SET1/COMPASS complexes

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In this study we report the first crystal structure of a DPY-30 motif from the human DPY-30L protein and that it exists as a homodimer One DPY-30L monomer consists of two short and flexible terminal helices linked by a short turn co-purifies with BRE2 and SDC1 of the yeast COMPASS H3K4 methyltransferase complex members 2 it raises the

Evolving Catalytic Properties of the MLL Family SET

Summary Methylation of histone H3 lysine-4 is a hallmark of chromatin associated with active gene expression The activity of H3K4-specific modification enzymes in higher eukaryotes the MLL (or KMT2) family is tightly regulated The MLL family has six members each with a specialized function All contain a catalytic SET domain that associates with a core multiprotein complex for activation

Structural and functional analysis of SET8 a histone

SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that is implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-adenosylhomocysteine

Structure and Conformational Dynamics of a

The methylation of histone 3 lysine 4 (H3K4) is carried out by an evolutionarily conserved family of methyltransferases referred to as complex of proteins associated with Set1 (COMPASS) The activity of the catalytic SET domain (su(var)3-9 enhancer-of-zeste and trithorax) is endowed through formin

Structural analysis of the core COMPASS family of

2011-12-7COMPASS composition and in vitro H3K4 methyltransferase activities were analyzed in the same way as (A) As a first step we investigated the effects of specific Cps subunits on in vitro H3K4 methylation by preparing full-length Set1 (1–1 080) with various Cps combinations ( Fig 1 A )

Crystal Structure of the COMPASS H3K4

2018-8-23To reveal the complete architecture of the yeast COMPASS catalytic module we co-expressed and purified the K lactis Set1 catalytic domain together with the full-length or near full-length Swd3 Swd1 Bre2 and Sdc1 proteins from insect cells (Figure 1A) The yeast COMPASS catalytic module displayed strong distributive H3K4 methyltransferase activity toward a reconstituted

Structure and Conformational Dynamics of a

2018-8-23To model the structure of the COMPASS subunits in the cryo-EM map we employed a combination of homology modeling secondary and tertiary structure prediction and de novo chain building (STAR Methods) Our modeling was also aided by the structure of the WD40 domain of Cps50 from Myceliophthola thermophila which we obtained by X-ray crystallography (Figure S3A)

Structural analysis of the core COMPASS family of

2011-12-7COMPASS composition and in vitro H3K4 methyltransferase activities were analyzed in the same way as (A) As a first step we investigated the effects of specific Cps subunits on in vitro H3K4 methylation by preparing full-length Set1 (1–1 080) with various Cps combinations ( Fig 1 A )

The role of set1 methylation of histone H3 lysine 4 on

COMPASS: A complex of proteins associated with a trithorax -related SET domain protein (2001) Correlation between histone lysine developmental changes at the chicken ~ Globin locus (2002) Crystal structure and functional analysis of the histone methyltransferase SET7/9 (1997) Crystal structure of the nucleosome core particle at 2 8 A

Structure and conformational dynamics of a

2018-8-23Structure of a COMPASS histone H3K4 methyltransferase complex Introduction Members of the Set1/MLL ( M ixed L ineage L eukemia) family of methyltransferases (KMT2) catalyze the methylation of Lysine 4 of histone H3 (H3K4) ( Piunti and Shilatifard 2016 Shilatifard 2012 )

Structural analysis of the core COMPASS family of histone

Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human Yoh-hei Takahashia 1 Gerwin H Westfieldb c 1 Austin N Oleskieb Raymond C Trievelc Ali Shilatifarda 2 and Georgios Skiniotisb c 2 aStowers Institute for Medical Research Kansas City MO 64110 bLife Sciences Institute University of Michigan Ann Arbor MI 48109 and cDepartment of

Loop

My earliest introduction to scientific research was as an undergraduate utilizing asymmetric catalysis to synthesize bioactive small-molecules After completing my bachelors and masters in Chemistry I decided to explore the interaction of protein complexes and their inhibitors as part of my doctoral studies at the University of Washington Seattle I developed chemical biology techniques to

Histone H3 lysine 4 methyltransferases and

2013-10-9Epigenetic mechanisms are fundamental to understanding the regulatory networks ofgene expression that govern stem cell maintenance and differentiation Methylated histone H3 lysine 4 (H3K4) has emerged as a key epigenetic signal forgene transcription it is dynamically modulated by several specific H3K4methyltransferases and demethylases

internal interaction in RBBP5 regulates assembly and

The yeast COMPASS complex adopts a Y-shaped structure in which Swd1 (an RBBP5 ortholog) and Swd3 (a WDR5 ortholog) form the two arms of the Y-shape Set1 sits at the central fork and Bre2 (an ASH2L ortholog) is located at the bottom of the Y-shape ( 13 14 )

Structural basis for COMPASS recognition of an H2B

H3K4 methylation in yeast is catalyzed by Set1 the methyltransferase subunit of COMPASS We report here the cryo-EM structure of a six-protein core COMPASS subcomplex which can methylate H3K4 and be stimulated by H2B-Ub bound to a ubiquitinated nucleosome

Crystal Structure of the COMPASS H3K4

Here we present the crystal structure of the intact yeast COMPASS histone methyltransferase catalytic module consisting of Swd1 Swd3 Bre2 Sdc1 and Set1 The complex is organized by Swd1 whose conserved C-terminal tail not only nucleates Swd3 and a Bre2-Sdc1 subcomplex but also joins Set1 to construct a regulatory pocket next to the

Structure and Conformational Dynamics of a

2020-7-31The methylation of histone 3 lysine 4 (H3K4) is carried out by an evolutionarily conserved family of methyltransferases referred to as complex of proteins associated with Set1 (COMPASS) The activity of the catalytic SET domain (su(var)3-9 enhancer-of-zeste and trithorax) is endowed through forming a complex with a set of core proteins that

Construction of hybrid yeast

Hsu PL Li H Lau HT Leonen C Dhall A et al (2018) Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module Cell 174: 1106-1116 e9 Wang Y Ding Z Liu X Bao Y Huang M et al (2018) Architecture and subunit arrangement of the complete Saccharomyces cerevisiae COMPASS complex Sci Rep 8:17405-018-35609-8

Histone H2BK123 monoubiquitination is the critical

The first H3K4 (histone H3 lysine 4) methylase Set1/COMPASS was isolated from Saccharomyces cerevisiae and was demonstrated to be capable of mono- di- and trimethylating H3K4 (Miller et al 2001 Roguev et al 2001 Krogan et al 2002) This posttranslational modification of H3K4 by COMPASS requires prior H2BK123 (histone H2B lysine 123) monoubiquitination in yeast and H2BK120 in

Structural implications of Dpy30 oligomerization for

The crystal structure of Dpy30C-Bre2 DBM contains two dimers of Dpy30C (chain A and B: AB dimer chain C and D: CD dimer) and only one copy of Bre2 DBM (chain E) in an asymmetrical unit (Fig 1D) The overall structure of the complex fits the electronic density well except the DBM peptide