Histone Methylation Participates in Gene Expression Control during the Early Development of the Pacific Oyster Crassostrea gigas

Abstract

Histone methylation patterns are important epigenetic regulators of mammalian development, notably through stem cell identity maintenance by chromatin remodeling and transcriptional control of pluripotency genes. But, the implications of histone marks are poorly understood in distant groups outside vertebrates and ecdysozoan models. However, the development of the Pacific oyster Crassostrea gigas is under the strong epigenetic influence of DNA methylation, and Jumonji histone-demethylase orthologues are highly expressed during C. gigas early life. This suggests a physiological relevance of histone methylation regulation in oyster development, raising the question of functional conservation of this epigenetic pathway in lophotrochozoan. Quantification of histone methylation using fluorescent ELISAs during oyster early life indicated significant variations in monomethyl histone H3 lysine 4 (H3K4me), an overall decrease in H3K9 mono- and tri-methylations, and in H3K36 methylations, respectively, whereas no significant modification could be detected in H3K27 methylation. Early in vivo treatment with the JmjC-specific inhibitor Methylstat induced hypermethylation of all the examined histone H3 lysines and developmental alterations as revealed by scanning electronic microscopy. Using microarrays, we identified 376 genes that were differentially expressed under methylstat treatment, which expression patterns could discriminate between samples as indicated by principal component analysis. Furthermore, Gene Ontology revealed that these genes were related to processes potentially important for embryonic stages such as binding, cell differentiation and development. These results suggest an important physiological significance of histone methylation in the oyster embryonic and larval life, providing, to our knowledge, the first insights into epigenetic regulation by histone methylation in lophotrochozoan development.

Changes in Genome-Wide Methylation and Gene Expression in Response to Future pCO2 Extremes in the Antarctic Pteropod Limacina helicina antarctica

“…Overall, our results suggest that differential methylation of DNA and histones may jointly influence persistent transcriptomic responses by L. helicina antarctica to future pCO 2 extremes. Histone modifications (e.g., histone methylation) and subsequent changes in transcription have been shown to regulate development and responses to environmental stress in molluscs (Fellous et al, 2015(Fellous et al, , 2019Gonzalez-Romero et al, 2017) and other calcifying marine invertebrates (Rodriguez-Casariego et al, 2018). Interactions between chromatin structure and DNA methylation should be explored in greater functional detail in this system in order to substantiate these observations and understand their influence on pervasive and persistent downregulation by L. helicina antarctica under OA.…”

The Epigenetics Dilemma

“…This would have been inconceivable only a couple of years ago. As a consequence, results presented in this issue and elsewhere make clear that this is a time of opportunity for epigenetics as its contours and impact are traced more and more clearly: the epigenome is demonstrated to be very plastic, it changes during development [2], but also, and in a different way, when exposed to external environmental cues. These changes occur sometimes within generations [3] and, in other cases, epigenetic plasticity occurs through generations [4,5], conveying parental effects of very different type (e.g., parental diet or hatchery environment).However, this plastic character of the epigenome makes it also difficult to draw general conclusions on how every epigenotype, genotype and phenotype are interrelated.…”

“…It is also shown that epigenetic modifications can be associated with the magnitude of change in reaction norms of some but not all phenotypic traits [6]. In addition, even when considering the same bearer of epigenetic information (e.g., DNA methylation), different organisms show different types of DNA methylation (e.g., [1][2][3][4][5][6]) with potentially different types of phenotypic effects. Nevertheless, epigenetic changes do not occur randomly along the genome.…”

“…First, it is the very definition of epigenetics (considered a "heritable but reversible changes in gene function"; paraphrased as e.g. "regulation of transcription" used in [2], "gene activation" by Gavery et al [4], and "gene expression" in [6]) that makes a clear and unambiguous claim of a link between epigenetics and gene function, i.e., the (molecular) phenotypes. Such a claim is absent from definitions of genetics ("Genetics is the study of heredity"; e.g., [9]) thus orphaning those changes in chromatin structure that do not lead to detectable changes in gene function.…”

Genome Survey of Chromatin-Modifying Enzymes in Threespine Stickleback: A Crucial Epigenetic Toolkit for Adaptation?

“…These studies were crucial to advances in cancer diagnostics and prognostics (Costa-pinheiro and Montezuma, 2015), to understanding of plant production and plant responses to the environment (Baulcombe and Dean, 2014;Wang and Köhler, 2017), and to understanding of the mechanistic basis of transgenerational epigenetic inheritance in mammals (Van Otterdijk and Michels, 2016). Importantly, recent studies of the DNA methyltransferase family have also revealed that changes in gene copy numbers and molecular interactions can modulate enzyme activity and their role in transcriptional regulation (Lyko, 2018), and that a vast diversity of epigenetic and transcriptional patterns during development are observed among species (Riviere et al, 2013;Eckersley-maslin et al, 2018;Fellous et al, 2018Fellous et al, , 2019cHorsfield, 2019;Vastenhouw et al, 2019). This diversity, coupled with a variable number of genes FIGURE 1 | Schmatic view of marine stickleback life cycle illustrating the potential for this species as a model to elucidate the synergistic role of epigenetic mechanisms in aquaculture and eco-evolutionary studies.…”