Redox-Dependent Chromatin Remodeling: A New Function of Nitric Oxide as Architect of Chromatin Structure in Plants

Abstract

Nitric oxide (NO) is a key signaling molecule in all kingdoms. In plants, NO is involved in the regulation of various processes of growth and development as well as biotic and abiotic stress response. It mainly acts by modifying protein cysteine or tyrosine residues or by interacting with protein bound transition metals. Thereby, the modification of cysteine residues known as protein S-nitrosation is the predominant mechanism for transduction of NO bioactivity. Histone acetylation on N-terminal lysine residues is a very important epigenetic regulatory mechanism. The transfer of acetyl groups from acetyl-coenzyme A on histone lysine residues is catalyzed by histone acetyltransferases. This modification neutralizes the positive charge of the lysine residue and results in a loose structure of the chromatin accessible for the transcriptional machinery. Histone deacetylases, in contrast, remove the acetyl group of histone tails resulting in condensed chromatin with reduced gene expression activity. In plants, the histone acetylation level is regulated by S-nitrosation. NO inhibits HDA complexes resulting in enhanced histone acetylation and promoting a supportive chromatin state for expression of genes. Moreover, methylation of histone tails and DNA are important epigenetic modifications, too. Interestingly, methyltransferases and demethylases are described as targets for redox molecules in several biological systems suggesting that these types of chromatin modifications are also regulated by NO. In this review article, we will focus on redox-regulation of histone acetylation/methylation and DNA methylation in plants, discuss the consequences on the structural level and give an overview where NO can act to modulate chromatin structure.

Keywords: S-nitrosation; acetylation; chromatin modulation; methylation; nitric oxide; redox-modification.

Figure 1

Schematic model of NO-induced chromatin modulation. Due to the activity of HDAs the chromatin is densely packed and genes are not transcribed. Upon formation of NO, the HDA-complexes become inhibited by S-nitrosation, leading to acetylation of the chromatin. This loosen chromatin structure allows transcription in tight interplay with activating transcription factors.

Figure 2

Alignment of the amino acid sequences of the HDA domain of human HDA2 and different plant histone deacetylase 6 and 19 proteins. HDA amino acid sequences were aligned using Clustal W. The HDA domain is depicted in green. Cysteine residues of human HDA2 which are targets for S-nitrosation and the corresponding cysteine residues of plant HDAs are highlighted in yellow. Other conserved cysteine residues are marked in blue. Hs, Homo sapiens NP_001518.3; Ath, Arabidospsis thaliana AED97705.1 (HDA6) and O22446.2 (HDA19); Aa, Artemisia annua PWA92260.1; Gm, Glycine max XP_003525556.1 (HDA6) and XP_003543935.1 (HDA19); Ha, Helianthus annuus XP_021978414.1; Jc, Jatropha curcas XP_012079994.1; Ls, Lactuca sativa XP_023740973.1; Ps, Papaver somniferum XP_026387130.1 (HDA6) and XP_026455725.1 (HDA19); Bv, Beta vulgaris XP_010690952.1; Mt., Medicago truncatula XP_013462369.1; Ns, Nicotiana sylvestris XP_009770456.1; Sb, Sorghum bicolor XP_002438614.1.

Figure 3

Comparison of HDA6, HDA19 and human HDA2 substrate binding site. Structural comparison between human HDA2 and Glycine max HDA6 and HDA19. The HDA domains of G. max HDA6 (amino acids 29–397, Uniprot entry I1MTD8) and of G. max HDA19 (amino acids 3–371, Uniprot entry A0A0R0H2W2) were modeled using the SwissProt Modeling server with human HDA2 as template (PDB entry 4LXZ). The histone deacetylase inhibitor octanedioic acid hydroxyamide phenylamide is highlighted in green and shows the location of the active site (mark with a red circle). Cysteine residues, which are located next to the active site are marked in yellow. These cysteine residues are targets for S-nitrosation in human HDA2.

Figure 4

NO-dependent regulation of chromatin modulation. Histone acetylation/methylation and DNA-methylation is controlled by different sets of acetylases/deacetylases (HATs/HDAs) and methyl transferases/demethylases (HMT/HDMs and DNA-MTs/DNA-DMs). NO can regulate the expression of some of these chromatin modifiers as well as their activity. Moreover, NO can affect the supply of the methyl group donor SAM and the level of the methyltransferase inhibitor SAH by altering the activity of enzymes of the methylation cycle and/or connected pathways. For more details see this paper.