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

Abstract

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.

Nitric Oxide Implication in Potato Immunity to Phytophthora infestans via Modifications of Histone H3/H4 Methylation Patterns on Defense Genes

“…Similar to histone acetylation, histone methylation is not a permanent modification, and both of these modifications often cooperate or antagonize. Although it has recently been documented by Rudolf et al [ 48 ] that the GSNOR function is also required for balancing the methylation index between the prominent methyl donor, S-adenosylmethionine (SAM), for histone or DNA methylation and S-adenosylhomocysteine (SAH), its byproduct (the SAM/SAH ratio). Finally, the authors postulated that GSNOR1 plays a crucial role in regulating methylation processes and stress-responsive gene expression [ 48 ].…”

“…There is no doubt that a peculiar crosstalk between methyltransferases/demethylases modifying histone patterns exists under stress conditions; however, there is no information on NO engagement in inhibiting JMJC domain-containing histone demethylases in plants. It was proposed that GSNO reductase (GSNOR) activity regulating the intracellular level of NO indirectly contributes to demethylation processes in Arabidopsis [ 48 ]. This finding aligns with our result, suggesting that GSNOR might control the NO level during biotic stress and indirectly affects histone methylation in orchestrating defense responses in potato.…”

“…The experimental evidence was focused on exploring NO regulation via the tyrosine nitration or S-nitrosation of histone deacetylases (HDACs), of which the downregulation enhances acetylation and makes chromatin more accessible for transcription factors [ 44 , 45 , 46 , 47 ]. A study on GSNOR1-mediated histone and DNA methylation has been published recently, revealing the complex picture involving a new NO function as an epigenetic mediator in plants [ 48 ].…”

Micrografting Provides Evidence for Systemic Regulation of Sulfur Metabolism between Shoot and Root

“…S-nitrosoglutathione is another sulfur-containing compound that has been suggested to be involved in shoot-to-root communication due to organ-specific dynamic inactivation by S-nitrosoglutathione reductase (GSNOR) [ 30 ]. GSNOR rapidly degrades S-nitrosoglutathione and controls the demethylation and expression of transposable elements and stress-responsive genes [ 31 ]. Remarkably, DNA demethylation of the SULTR1;1 promotor also triggers the expression of SULTR1;1 and is responsive to external sulfur supply [ 32 ].…”

Plant homocysteine, a methionine precursor and plant’s hallmark of metabolic disorders

“…It is worth noting that the maintenance of the AdoMet/AdoHcy ratio is considered a metabolic hallmark of the cellular methylation potential or methylation index (Hoffman et al, 1979;Moffatt and Weretilnyk, 2001;Kocsis et al, 2003). As indicated by Rudolf et al (2021), AdoMet homeostasis, and thus balancing the AdoMet/AdoHcy ratio, depends on S-nitrosoglutathione reductase (GSNOR1). This enzyme controls the level of the Snitrosoglutathione and S-nitrosation reactions in plant cells.…”