Direct interrogation of the role of H3K9 in metazoan heterochromatin function DOI Open Access

Taylor J.R. Penke,

Daniel J. McKay, Brian D. Strahl

и другие.

Genes & Development, Год журнала: 2016, Номер 30(16), С. 1866 - 1880

Опубликована: Авг. 15, 2016

A defining feature of heterochromatin is methylation Lys9 histone H3 (H3K9me), a binding site for protein 1 (HP1). Although H3K9 methyltransferases and HP1 are necessary proper structure, the specific contribution to function animal development unknown. Using our recently developed platform engineer genes in Drosophila, we generated H3K9R mutant flies, separating functions nonhistone substrates methyltransferases. Nucleosome occupancy HP1a at pericentromeric markedly decreased mutants. Despite these changes chromosome architecture, small percentage mutants complete development. Consistent with this result, expression most protein-coding genes, including those within heterochromatin, similar between controls. In contrast, exhibit increased open chromatin transcription from piRNA clusters transposons, resulting transposon mobilization. Hence, silencing major developmental H3K9.

Язык: Английский

Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease DOI
Kamakoti P. Bhat, H. Ümit Kanıskan, Jian Jin

и другие.

Nature Reviews Drug Discovery, Год журнала: 2021, Номер 20(4), С. 265 - 286

Опубликована: Янв. 19, 2021

Язык: Английский

Процитировано

180

Histone editing elucidates the functional roles of H3K27 methylation and acetylation in mammals DOI
Aditya Sankar,

Faizaan Mohammad,

Arun Kumar Sundaramurthy

и другие.

Nature Genetics, Год журнала: 2022, Номер 54(6), С. 754 - 760

Опубликована: Июнь 1, 2022

Язык: Английский

Процитировано

107

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body DOI Creative Commons
Robert J. Duronio, William F. Marzluff

RNA Biology, Год журнала: 2017, Номер 14(6), С. 726 - 738

Опубликована: Янв. 6, 2017

Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of pre-mRNA. The for all 5 proteins clustered metazoans and coordinately regulated with high levels expression during S phase. Production occurs nuclear body called Histone Locus Body (HLB), subdomain nucleus defined concentration factors necessary gene transcription pre-mRNA processing. include scaffolding protein NPAT, essential transcription, FLASH U7 snRNP, both activated Cyclin E/Cdk2-mediated phosphorylation NPAT at G1-S transition. within HLB couples processing, enhancing efficiency mRNA biosynthesis.

Язык: Английский

Процитировано

132

Understanding histone H3 lysine 36 methylation and its deregulation in disease DOI
Jie Li, Jeong Hyun Ahn, Gang Greg Wang

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2019, Номер 76(15), С. 2899 - 2916

Опубликована: Май 30, 2019

Язык: Английский

Процитировано

121

DNA binding by PHF1 prolongs PRC2 residence time on chromatin and thereby promotes H3K27 methylation DOI
Jeongyoon Choi,

Andreas Bachmann,

Katharina Tauscher

и другие.

Nature Structural & Molecular Biology, Год журнала: 2017, Номер 24(12), С. 1039 - 1047

Опубликована: Окт. 19, 2017

Язык: Английский

Процитировано

119

Shaping the cellular landscape with Set2/SETD2 methylation DOI

Stephen L. McDaniel,

Brian D. Strahl

Cellular and Molecular Life Sciences, Год журнала: 2017, Номер 74(18), С. 3317 - 3334

Опубликована: Апрель 6, 2017

Язык: Английский

Процитировано

118

The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity DOI

Kenneth D. Bromberg,

Taylor R. H. Mitchell,

Anup K. Upadhyay

и другие.

Nature Chemical Biology, Год журнала: 2017, Номер 13(3), С. 317 - 324

Опубликована: Янв. 23, 2017

Язык: Английский

Процитировано

112

Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3 DOI Creative Commons
Ksenia Finogenova, Jacques Bonnet, Simon Poepsel

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Ноя. 19, 2020

Repression of genes by Polycomb requires that PRC2 modifies their chromatin trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure dinucleosomes reveals how binding its catalytic subunit EZH2 to nucleosomal DNA orients N-terminus via an extended network interactions place H3K27 into site. Unmodified occupies a critical position in EZH2-DNA interface. Mutation arginine or alanine inhibits methylation nucleosomes vitro . Accordingly, Drosophila H3K36A H3K36R mutants show reduced levels H3K27me3 defective repression HOX genes. The relay between EZH2, therefore creates geometry permits allosteric inhibition methylated chromatin.

Язык: Английский

Процитировано

103

Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC DOI Open Access
Felice Frey, Thomas W. Sheahan,

Katja Finkl

и другие.

Genes & Development, Год журнала: 2016, Номер 30(9), С. 1116 - 1127

Опубликована: Май 1, 2016

Polycomb group (PcG) protein complexes repress transcription by modifying target gene chromatin. In Drosophila, this repression requires association of PcG with cis-regulatory response elements (PREs), but the interactions permitting formation these assemblies are poorly understood. We show that Sfmbt subunit DNA-binding Pho-repressive complex (PhoRC) and Scm canonical Polycomb-repressive 1 (PRC1) directly bind each other through their SAM domains. The 1.9 Å crystal structure Scm-SAM:Sfmbt-SAM reveals recognition mechanism shows Sfmbt-SAM lacks polymerization capacity domains its PRC1 partner subunit, Ph. Functional analyses in Drosophila demonstrate Scm-SAM essential for PhoRC DNA binding is critical to initiate PREs. Together, suggests PRE-tethered nucleates recruitment Scm-SAM/Ph-SAM-mediated then results PRC1-compacted

Язык: Английский

Процитировано

87

Intergenerationally Maintained Histone H4 Lysine 16 Acetylation Is Instructive for Future Gene Activation DOI Creative Commons
Maria Samata,

Anastasios Alexiadis,

Gautier Richard

и другие.

Cell, Год журнала: 2020, Номер 182(1), С. 127 - 144.e23

Опубликована: Июнь 4, 2020

Язык: Английский

Процитировано

84