Roles and regulation of histone methylation in animal development

Nature Reviews Molecular Cell Biology, Год журнала: 2019, Номер 20(10), С. 625 - 641

Опубликована: Июль 2, 2019

Язык: Английский

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Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks

Cell, Год журнала: 2020, Номер 184(1), С. 120 - 132.e14

Опубликована: Дек. 10, 2020

Язык: Английский

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Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors

Cell, Год журнала: 2018, Номер 175(1), С. 186 - 199.e19

Опубликована: Сен. 1, 2018

Язык: Английский

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50+ years of eukaryotic transcription: an expanding universe of factors and mechanisms

Nature Structural & Molecular Biology, Год журнала: 2019, Номер 26(9), С. 783 - 791

Опубликована: Авг. 22, 2019

Язык: Английский

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Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation

Genes & Development, Год журнала: 2018, Номер 32(3-4), С. 202 - 223

Опубликована: Фев. 1, 2018

Enhancers are important genomic regulatory elements directing cell type-specific transcription. They assume a key role during development and disease, their identification functional characterization have long been the focus of scientific interest. The advent next-generation sequencing clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based genome editing has revolutionized means by which we study enhancer biology. In this review, cover recent developments in prediction enhancers based on chromatin characteristics reporter assays endogenous DNA perturbations. We discuss that two latter approaches provide different complementary insights, especially assessing sufficiency necessity for transcription activation. Furthermore, insights into mechanistic aspects function, including findings about cofactor requirements post-translational histone modifications such as monomethylation H3 Lys4 (H3K4me1). Finally, survey how these advance our understanding regulation with respect to promoter specificity transcriptional bursting an outlook covering open questions promising developments.

Язык: Английский

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The cancer driver genes IDH1/2, JARID1C/ KDM5C, and UTX/ KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism

Experimental & Molecular Medicine, Год журнала: 2019, Номер 51(6), С. 1 - 17

Опубликована: Июнь 1, 2019

Recent studies on mutations in cancer genomes have distinguished driver from passenger mutations, which occur as byproducts of development. The genome atlas (TCGA) project identified 299 genes and 24 pathways/biological processes that drive tumor progression (Cell 173: 371-385 e318, 2018). Of the genes, 12 are involved histones, histone methylation, demethylation. Among these those encoding demethylases JARID1C/KDM5C UTX/KDM6A were genes. Furthermore, gain-of-function metabolic enzymes, such isocitrate dehydrogenases (IDH)1/2, by producing an oncometabolite, D-2-hydroxyglutarate (D-2HG), is a competitive inhibitor α-ketoglutarate, O2-dependent dioxygenases Jumonji domain-containing demethylases, DNA demethylases. Studies oncometabolites suggest mediate changes chromatin structure. We reviewed most recent findings regarding cancer-specific reprogramming tumor-suppressive roles UTX/KDM6A. also discussed other isoforms JARID1A, 1B, 1D KDM5 subfamilies JMJD3/KDM6B KDM6 subfamilies, play opposing oncogenes or suppressors depending cell type. Genes removal methyl groups histones associated with can promote suppress growth status cell. Hyunsung Park colleagues at University Seoul, South Korea, review current knowledge two been Cancer Genome Atlas Because demethylase enzymes rely cellular metabolites to function, their effect influenced conditions microenvironment low oxygen. mechanisms through methylation affect expression remain unknown. Further understanding how metabolism affects modification will help guide development more effective treatments.

Язык: Английский

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KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer

Cancer Cell, Год журнала: 2020, Номер 37(4), С. 599 - 617.e7

Опубликована: Апрель 1, 2020

Язык: Английский

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Ferroptosis is governed by differential regulation of transcription in liver cancer

Redox Biology, Год журнала: 2019, Номер 24, С. 101211 - 101211

Опубликована: Май 10, 2019

Ferroptosis is an outcome of metabolic disorders and closely linked to liver cancer. However, the mechanism underlying fine regulation ferroptosis in cancer remains unclear. Here, we have identified two categories genes: up-regulated factors (FUF) down-regulated (FDF), which stimulate suppress by affecting synthesis GSH. Furthermore, FUF are controlled one transcription factor HIC1, while FDF another HNF4A. Occurrence might depend on histone acetyltransferase KAT2B. Upon stimulation ferroptosis, dissociation KAT2B prevents HNF4A from binding promoter. This effect happens prior recruitment promoter, facilitates HIC1 transcribe FUF. Clinically, conversely correlate with tumor stage Patients lower higher exhibit poorer prognostic outcomes. Disrupting balance between be helpful treating • Opposite gene expression profiles trigged identified. Reduction GSH major cause inducing cells. Genes related Stimulation breaks Lower has clinical outcomes patients.

Язык: Английский

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UTX condensation underlies its tumour-suppressive activity

Nature, Год журнала: 2021, Номер 597(7878), С. 726 - 731

Опубликована: Сен. 15, 2021

Язык: Английский

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Histone acetyltransferases CBP/p300 in tumorigenesis and CBP/p300 inhibitors as promising novel anticancer agents

Theranostics, Год журнала: 2022, Номер 12(11), С. 4935 - 4948

Опубликована: Янв. 1, 2022

The histone acetyltransferases CBP and p300, often referred to as CBP/p300 due their sequence homology functional overlap co-operation, are emerging critical drivers of oncogenesis in the past several years.CBP/p300 induces H3 lysine 27 acetylation (H3K27ac) at target gene promoters, enhancers super-enhancers, thereby activating transcription.While earlier studies indicate that deletion/loss can promote tumorigenesis, have more recently been shown be over-expressed cancer cells drug-resistant cells, activate oncogene transcription induce cell proliferation, survival, metastasis, immune evasion drug-resistance.Small molecule acetyltransferase inhibitors, bromodomain BET dual inhibitors p300 protein degraders discovered.The reduce H3K27ac, down-regulate transcription, growth inhibition death, response, overcome drug resistance suppress tumor progression vivo.In addition, enhance anticancer efficacy chemotherapy, radiotherapy epigenetic agents, including inhibitors; combination therapies exert substantial effects mouse models human cancers cancers.Currently, two under clinical evaluation patients with advanced solid tumors or hematological malignancies.In summary, identified tumorigenic drivers, promising novel agents for translation.

Язык: Английский

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