Nitric oxide is an epigenetic regulator of gene expression by directly controlling DNA methylation patterns

Bovee, Rhea C.; Pham, Vy; Fernandez, Jenna; Tretyakova, Natalia; Thomas, Douglas D.

doi:10.1016/j.freeradbiomed.2018.04.375

Cited by 7 publications

(4 citation statements)

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“…It was documented that a NO donor (DETA/NO) could inhibit the catalytic activity in vitro and the expression level of JMJC domain-containing histone demethylase (KDM3A) in a dose-dependent manner (Hickok et al, 2013). A similar effect was found when TET enzyme activity significantly decreased in cancer cells exposed to NO, supported by EPR studies showing that NO could directly bind to catalytic non-heme iron (Bovee et al, 2018).…”

Section: Genes Of the Rddm Pathway Responsive To Nitric Oxide Are Inv...mentioning

confidence: 84%

“…Studies, which have been conducted for many years on mammals, provide essential insights into how NO can inhibit mononuclear non-heme iron dioxygenases enzymes, such as histone Jumonji C demethylases (JMJC) and DNA demethylase (Ten Eleven Translocation-TET) by producing a nitrosyl-iron complex in the active pocket of the enzyme or via formation of dinitrosyliron complexes (DNICs) that reduce the iron cofactor availability ( Hickok et al., 2013 ; Cheng et al., 2014 ; Bovee et al., 2018 ; Palczewski et al., 2019 ). It was documented that a NO donor (DETA/NO) could inhibit the catalytic activity in vitro and the expression level of JMJC domain-containing histone demethylase (KDM3A) in a dose-dependent manner ( Hickok et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

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Insights into the expression of DNA (de)methylation genes responsive to nitric oxide signaling in potato resistance to late blight disease

et al. 2022

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Our previous study concerning the pathogen-induced biphasic pattern of nitric oxide (NO) burst revealed that the decline phase and a low level of NO, due to S-nitrosoglutathione reductase (GSNOR) activity, might be decisive in the upregulation of stress-sensitive genes via histone H3/H4 methylation in potato leaves inoculated with avr P. infestans. The present study refers to the NO-related impact on genes regulating DNA (de)methylation, being in dialog with histone methylation. The excessive amounts of NO after the pathogen or GSNO treatment forced the transient upregulation of histone SUVH4 methylation and DNA hypermethylation. Then the diminished NO bioavailability reduced the SUVH4-mediated suppressive H3K9me2 mark on the R3a gene promoter and enhanced its transcription. However, we found that the R3a gene is likely to be controlled by the RdDM methylation pathway. The data revealed the time-dependent downregulation of the DCL3, AGO4, and miR482e genes, exerting upregulation of the targeted R3a gene correlated with ROS1 overexpression. Based on these results, we postulate that the biphasic waves of NO burst in response to the pathogen appear crucial in establishing potato resistance to late blight through the RdDM pathway controlling R gene expression.

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Section: Genes Of the Rddm Pathway Responsive To Nitric Oxide Are Inv...mentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Insights into the expression of DNA (de)methylation genes responsive to nitric oxide signaling in potato resistance to late blight disease

et al. 2022

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“…In this context, elevated levels of SAM, as observed in gsnor1-3 (Figure 1A), counteract active DNA demethylation in human cells [89,101]. Further, mammalian TET enzymes involved in DNA demethylation are inhibited by • NO due to the formation of a nitrosyl-iron complex with their catalytic iron [102]. Similarly, the iron-sulfur-containing ROS1/DME DNA demethylases [103] could be affected by • NO in gsnor1-3.…”

Section: Gsnor1 Function Is Crucial For the Maintenance Of Histone Me...mentioning

confidence: 89%

GSNOR Contributes to Demethylation and Expression of Transposable Elements and Stress-Responsive Genes

et al. 2021

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In the past, reactive nitrogen species (RNS) were supposed to be stress-induced by-products of disturbed metabolism that cause oxidative damage to biomolecules. However, emerging evidence demonstrates a substantial role of RNS as endogenous signals in eukaryotes. In plants, S-nitrosoglutathione (GSNO) is the dominant RNS and serves as the •NO donor for S-nitrosation of diverse effector proteins. Remarkably, the endogenous GSNO level is tightly controlled by S-nitrosoglutathione reductase (GSNOR) that irreversibly inactivates the glutathione-bound NO to ammonium. Exogenous feeding of diverse RNS, including GSNO, affected chromatin accessibility and transcription of stress-related genes, but the triggering function of RNS on these regulatory processes remained elusive. Here, we show that GSNO reductase-deficient plants (gsnor1-3) accumulate S-adenosylmethionine (SAM), the principal methyl donor for methylation of DNA and histones. This SAM accumulation triggered a substantial increase in the methylation index (MI = [SAM]/[S-adenosylhomocysteine]), indicating the transmethylation activity and histone methylation status in higher eukaryotes. Indeed, a mass spectrometry-based global histone profiling approach demonstrated a significant global increase in H3K9me2, which was independently verified by immunological detection using a selective antibody. Since H3K9me2-modified regions tightly correlate with methylated DNA regions, we also determined the DNA methylation status of gsnor1-3 plants by whole-genome bisulfite sequencing. DNA methylation in the CG, CHG, and CHH contexts in gsnor1-3 was significantly enhanced compared to the wild type. We propose that GSNOR1 activity affects chromatin accessibility by controlling the transmethylation activity (MI) required for maintaining DNA methylation and the level of the repressive chromatin mark H3K9me2.

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“…These studies highlighted that PTC has one of the lowest frequency of DNA methylation alterations [73], while ATC exhibits a frequency of DNA methylation alterations which was 10 fold that of PTC [74] Nitrate exposition with the consequent NO overproduction could represent of the causes of alterations in methylation levels: NO treatment on cancer cell lines was shown to induce alteration of methylation patterns although the epigenetic effects through DNA methylation were diverse and contradictory in different lines [75]. A recent paper [76] suggested that NO may interfere with methylation patterns by inhibiting the different isoforms of ten-eleven translocation (TET) enzymes, which are responsible of the active removal of methyl group via the catalysis of 5-methylcytosine (5mC) oxidation to 5-hydroxy-(5hmC), 5-formly, and 5-carboxy [77,78]. Moreover, NO can affect another class of epigenetic modifications that were found to be associated with the insurgence and aggressiveness of tumors: modifications of the histone tails [79][80][81].…”

Section: Thyroid Cancermentioning

confidence: 99%

New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way

Pitto

Gorini

Bianchi

et al. 2020

IJERPH

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In recent years, the presence in the environment of chemical compounds with thyroid-disrupting effects is progressively increased. This phenomenon has risen concern for human health as the preservation of thyroid system homeostasis is essential for fetal development and for maintaining psychological and physiological wellbeing. An increasing number of studies explored the role of different classes of toxicants in the occurrence and severity of thyroid diseases, but large epidemiological studies are limited and only a few animal or in vitro studies have attempted to identify the mechanisms of chemical action. Recently, epigenetic changes such as alteration of methylation status or modification of non-coding RNAs have been suggested as correlated to possible deleterious effects leading to different thyroid disorders in susceptible individuals. This review aims to analyze the epigenetic alterations putatively induced by chemical exposures and involved in the onset of frequent thyroid diseases such as thyroid cancer, autoimmune thyroiditis and disruption of fetal thyroid homeostasis.

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Nitric oxide is an epigenetic regulator of gene expression by directly controlling DNA methylation patterns

Cited by 7 publications

References 0 publications

Insights into the expression of DNA (de)methylation genes responsive to nitric oxide signaling in potato resistance to late blight disease

Insights into the expression of DNA (de)methylation genes responsive to nitric oxide signaling in potato resistance to late blight disease

GSNOR Contributes to Demethylation and Expression of Transposable Elements and Stress-Responsive Genes

New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way

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