Oxidative Stress Signaling to Chromatin in Health and Disease

Figures & data

Figure 1. Causes and consequences of elevated nuclear and cytoplasmic reactive oxygen species.

Many pathogenic factors and pathophysiological processes lead to an increase in cytoplasmic and nuclear ROS. ROS can be detoxified, function as second messengers or damaging agents, altering gene expression, inducing mutagenesis or cell death.

Stars indicate macromolecular damage.

3-DG: 3-deoxyglucosone; Ang II: Angiotensin II; CAT: Catalase; COX: Cyclooxygenase; ER: Endoplasmic reticulum; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GSH: Glutathione; LOX: Lipoxygenase; NO: Nitric oxide; NOS: Nitric oxide synthase; NOX: NADPH oxidase; PRDX: Peroxiredoxin; ROS: Reactive oxygen species; SOD: Superoxide dismutase; SOD*: Mutated SOD; TF: Transcription factor; TRX: Thioredoxin.

Figure 2. Oxidative stress induces direct modifications of chromatin.

(A) Different oxidative histone modifications lead to alterations of chromatin structure. (B) Oxidation of deoxyguanine directly influences gene expression.

GS: Reduced glutathione; GSH: Glutathione; GSSG: Glutathione disulfide; NO: Nitric oxide; ROS: Reactive oxygen species; TF: Transcription factor.

Figure 3. Oxidative stress influences chromatin modifiers.

Chromatin modifying enzymes can be inhibited under oxidative stress conditions by different mechanisms, including SAM depletion, oxidation, carbonylation or nitration. Activation of DNA methylation is mediated by oxidative DNA damage and the SIRT1 HDAC can be stimulated by LDH.

DNMT: DNA methyltransferase; GSH: Glutathione; HDAC: Histone deacetylase; HMT: Histone methyltransferase; LDH: Lactate dehydrogenase; MAT: Methionine adenosyltransferase; MS: Methionine synthase; NAD+: Nicotinamide adenine dinucleotide; NO: Nitric oxide; ROS: Reactive oxygen species; SAM: S-adenosylmethionine; TET: Ten-Eleven-Translocation DNA demethylase.

Figure 4. Effects of oxidative stress on different chromatin proteins.

(A) Regulation of TRIM28 by oxidative stress. (B) Influence of oxidative stress on functions of HMGB1. (C) Regulation of chromatin proteins by PI(5)P.

PI(5)P: Phosphatidylinositol-5-phosphate; ROS: Reactive oxygen species; TF: Transcription factor.