Function of Histones and Variants in Chromatin Remodeling: A Case Study of Spermatogenesis in Aquatic Animals

Abstract

Epigenetics refers to heritable changes that do not affect DNA sequences. Compared to genetic changes, epigenetic changes affect gene expression and protein products in cells, and these changes are reversible and dependent on the environment. There are three major types of epigenetic changes: DNA methylation, histone post-translational modifications (PTMs) increase the functional diversity of the proteome through the covalent addition of functional groups or proteins, proteolytic cleavage of regulatory subunits, or degradation of whole proteins), and non-coding Ribonucleic Acid.. This study focused on post-translational histone modifications.There are five main histone types: H1/H5, H2A, H2B, H3, and H4. Genes encoding histones do not contain introns and are among the most conserved proteins in eukaryotes. Histones are basic structural proteins comprising eukaryotic chromosomes. Generally, two molecules, H2A, H2B, H3, and H4 form a histone octamer that combines with DNA to form a structural unit called a nucleosome. This nucleosome appears every 200 bp and is connected by H1 histones to form chromatin.Histone modification refers to the addition of functional groups to histone tails, most commonly lysines. This process regulates gene expression by altering chromatin structure through condensation and depolymerization. Additionally, histone modification creates binding sites for various proteins. Histone modifications reported in animals include methylation, acetylation, phosphorylation, ubiquitination, SUMOylation (which is a small ubiquitin-related modifier involved in post-translational modification of proteins), ADP-ribosylation (which is a small ubiquitin-related modifier involved in post-translational modification of proteins), and short-chain lysine acylation.Many studies have shown that chromatin remodeling is a key step in spermatogenesis, involving the transformation of histones to protamines. Briefly, protamine replacement requires (Ⅰ) histone PTMs to promote the opening of histone-based chromatin structures, especially histone hyperacetylation and incorporation into histone variants; (Ⅱ) binding of bromine domain proteins to acetyl residues and remodeling of chromatin; (Ⅲ) formation and repair of DNA strand breaks in chromatin remodeling; and (Ⅳ) incorporation of protamine. Herein, we focused on Process (Ⅰ).In bisexual reproduction, sperm, as a paternal information carrier, is a key factor in a species continuation. Spermatogenesis includes various stages, including spermatogonia, primary and secondary spermatocytes, round sperms, and mature sperms. During round sperm transformation into mature sperm, chromatin remodeling occurs and cell morphology undergoes dramatic changes, in which histone PTMs and variants are essential. Histone PTMs patterns affect gene expression over a wide range, such as methylation, which is mainly related to gene expression activation or inhibition; acetylation, which activates transcriptional activity and participates in histone deposition and DNA repair; phosphorylation, which promotes post-transcriptional modification or participates in DNA double-strand break repair; and ubiquitin, which regulates various protein substrates in different cellular pathways. Histone variants have special functions in regulating chromosome structure. For example, histone H1 variants inhibit transcription during differentiation, histone H2A and H2B variants play a unique role in sperm chromatin packaging, H3.3 is the most important variant of H3, which is expressed in all stages of the cell cycle and participates in chromosome formation outside the S phase, Histone H4 is one of the slowest evolving proteins, and no histone variant has ever been found. Focusing on post-translational histone modifications, this study reviews the latest progress in methylation, acetylation, phosphorylation, and ubiquitination. Subsequently, the histone variants and their functions in chromatin remodeling are summarized. Finally, using Cynoglossus semilaevis as an example, this study briefly introduces the implications of these studies on spermatogenesis in aquatic animals. Elucidating the effect of PTMs on spermatogenesis will aid in exploring the regulatory mechanism of specific sperm (W-type) absence, which expands the fundamental theory of reproductive biology and provides novel solutions to monosex fry cultivation in aquaculture.

Keywords

• histone
• post-translational modification
• chromatin remodeling
• spermatogenesis