Dynamic DNA methylation: In the right place at the right time

Science, Journal Year: 2018, Volume and Issue: 361(6409), P. 1336 - 1340

Published: Sept. 28, 2018

The classical model of cytosine DNA methylation (the presence 5-methylcytosine, 5mC) regulation depicts this covalent modification as a stable repressive regulator promoter activity. However, whole-genome analysis 5mC reveals widespread tissue- and cell type–specific patterns pervasive dynamics during mammalian development. Here we review recent findings that delineate functions in developmental stages diverse genomic compartments well discuss the molecular mechanisms connect transcriptional 5mC. Beyond newly appreciated dynamics, regulatory roles for have been suggested new biological contexts, such learning memory or aging. use single-cell measurement techniques precise editing tools will enable functional analyses gene expression, clarifying its role various processes.

Language: Английский

---

Molecular mechanisms of transgenerational epigenetic inheritance

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(6), P. 325 - 341

Published: Jan. 4, 2022

Language: Английский

---

Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy

European Journal of Pharmacology, Journal Year: 2018, Volume and Issue: 837, P. 8 - 24

Published: Aug. 18, 2018

Language: Английский

---

Sensitivity of transcription factors to DNA methylation

Essays in Biochemistry, Journal Year: 2019, Volume and Issue: 63(6), P. 727 - 741

Published: Nov. 22, 2019

Abstract Dynamic binding of transcription factors (TFs) to regulatory elements controls transcriptional states throughout organism development. Epigenetics modifications, such as DNA methylation mostly within cytosine-guanine dinucleotides (CpGs), have the potential modulate TF DNA. Although has long been thought repress binding, a more recent model proposes that can also inhibit methylation. Here, we review possible scenarios by which and affect each other. Further in vivo experiments will be required generalize these models.

Language: Английский

---

Epigenetics in cancer: Fundamentals and Beyond

Pharmacology & Therapeutics, Journal Year: 2017, Volume and Issue: 173, P. 118 - 134

Published: Feb. 8, 2017

Language: Английский

---

Epigenetic Alterations in the Gastrointestinal Tract: Current and Emerging Use for Biomarkers of Cancer

Gastroenterology, Journal Year: 2020, Volume and Issue: 160(3), P. 690 - 709

Published: Dec. 4, 2020

Language: Английский

---

MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program

Science Advances, Journal Year: 2021, Volume and Issue: 7(1)

Published: Jan. 1, 2021

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic mice following bleomycin (BLM)-induced PF are characterized by altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion Mbd2 macrophages protected against BLM-induced PF. deficiency significantly attenuated transforming growth factor-β1 (TGF-β1) production reduced M2 macrophage accumulation BLM induction. Mechanistically, selectively bound to Ship promoter macrophages, which it repressed enhanced PI3K/Akt signaling promote program. Therefore, intratracheal administration liposomes loaded siRNA injuries fibrosis. Together, our data support possibility MBD2 could be a viable target clinical settings.

Language: Английский

---

Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

---

Epigenetics of Alzheimer’s Disease

Biomolecules, Journal Year: 2021, Volume and Issue: 11(2), P. 195 - 195

Published: Jan. 30, 2021

There are currently no validated biomarkers which can be used to accurately diagnose Alzheimer's disease (AD) or distinguish it from other dementia-causing neuropathologies. Moreover, date, only symptomatic treatments exist for this progressive neurodegenerative disorder. In the search new, more reliable and potential therapeutic options, epigenetic modifications have emerged as important players in pathogenesis of AD. The aim article was provide a brief overview current knowledge regarding role epigenetics (including mitoepigenetics) AD, possibility applying these advances future AD therapy. Extensive research has suggested an DNA methylation hydroxymethylation, histone posttranslational modifications, non-coding RNA regulation (with emphasis on microRNAs) course development Recent studies also indicated mitochondrial (mtDNA) interesting biomarker since dysfunctions mitochondria lower mtDNA copy number been associated with pathophysiology. evidence suggests that changes successfully detected, not central nervous system, but cerebrospinal fluid periphery, contributing further their both targets

Language: Английский

---

Evidence that direct inhibition of transcription factor binding is the prevailing mode of gene and repeat repression by DNA methylation

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(12), P. 1895 - 1906

Published: Dec. 1, 2022

Cytosine methylation efficiently silences CpG-rich regulatory regions of genes and repeats in mammalian genomes. To what extent this entails direct inhibition transcription factor (TF) binding versus indirect via recruitment methyl-CpG-binding domain (MBD) proteins is unclear. Here we show that combinatorial genetic deletions all four with functional MBDs mouse embryonic stem cells, derived neurons or a human cell line do not reactivate methylated promoters. These do, however, become activated by methylation-restricted TFs if DNA removed. We identify several causal neurons, including ONECUT1, which sensitive only at motif variant. Rampantly upregulated retrotransposons methylation-free feature CRE motif, activates them the absence methylation-sensitive CREB1. Our study reveals vivo argues inhibition, rather than repression tested MBD proteins, prevailing mechanism methylation-mediated repeats.

Language: Английский

---