Who Rules the Cell? An Epi-Tale of Histone, DNA, RNA, and the Metabolic Deep State

Abstract

Epigenetics refers to the mode of inheritance independent of mutational changes in the DNA. Early evidence has revealed methylation, acetylation, and phosphorylation of histones, as well as methylation of DNA as part of the underlying mechanisms. The recent awareness that many human diseases have in fact an epigenetic basis, due to unbalanced diets, has led to a resurgence of interest in how epigenetics might be connected with, or even controlled by, metabolism. The Next-Generation genomic technologies have now unleashed torrents of results exposing a wondrous array of metabolites that are covalently attached to selective sites on histones, DNA and RNA. Metabolites are often cofactors or targets of chromatin-modifying enzymes. Many metabolites themselves can be acetylated or methylated. This indicates that the acetylome and methylome can actually be deep and pervasive networks to ensure the nuclear activities are coordinated with the metabolic status of the cell. The discovery of novel histone marks also raises the question on the types of pathways by which their corresponding metabolites are replenished, how they are corralled to the specific histone residues and how they are recognized. Further, atypical cytosines and uracil have also been found in eukaryotic genomes. Although these new and extensive connections between metabolism and epigenetics have been established mostly in animal models, parallels must exist in plants, inasmuch as many of the basic components of chromatin and its modifying enzymes are conserved. Plants are chemical factories constantly responding to stress. Plants, therefore, should lend themselves readily for identifying new endogenous metabolites that are also modulators of nuclear activities in adapting to stress.

Biological Prescience: The Role of Anticipation in Organismal Processes

“…If these marks are maintained in offspring or new cells, they can direct gene expression in adaptive ways. Because these marks serve as a sort of memory of expressional states, they are better candidates for carrying out anticipatory functions (Jaenisch and Bird, 2003;Angers et al, 2010;Bollati and Baccarelli, 2020;Leung and Gaudin, 2020). Gene methylation and histone modifications are the two most well-studied epigenetic marks, and while the causal relationship between gene expression and alterations to these marks are still ambiguous, the correlative patterns between them are reasonably consistent (Holliday, 1990(Holliday, , 2006Karlić et al, 2010;Deans and Maggert, 2015).…”

Telomeres and Subtelomeres Dynamics in the Context of Early Chromosome Interactions During Meiosis and Their Implications in Plant Breeding

“…More recent studies have revealed a complex and dynamic landscape of histone posttranslational modifications (PTMs) with multiple modifications added and removed from the same histone tail of the same nucleosome (Lee et al, 2010). The overall PTMs state of histones has a deep impact in chromatin architecture, and in turn in metabolism, cell differentiation, development, and response to environmental changes and stress conditions (Leung and Gaudin, 2020).…”

Grape ASR-Silencing Sways Nuclear Proteome, Histone Marks and Interplay of Intrinsically Disordered Proteins

“…ASR proteins, at the example of VvMSA, are expressed in the transitions between different stages of plant development and in plant responses to environmental cues, mediated by complex interplay of endogenous (hormonal and metabolic) and exogenous signals [21]. Each of these respective developmental transitions and adaptive responses is subject to strong metabolic changes, transduced by specific epigenetic modifications and consequent differential expression of distinct sets of genes (recently reviewed by Leung and Gaudin, 2020) [42]. In plants, the genes encoding transcription factors are favorite targets of epigenetic regulations, and are considered to represent nearly 15% of all protein coding genes.…”