Journal Article

Epigenetic events in mammalian germ-cell development: reprogramming and beyond

Matsui, Yasuhisa, Sasaki, Hiroyuki

2008

Overview

Key Points Accumulating evidence indicates that epigenetic modifiers have key roles in genome-wide reprogramming and activation and repression of specific genes during mammalian germ-cell development. Germ-cell specification and suppression of the somatic gene expression programme might involve epigenetic modifications. Furthermore, differentiating primordial germ cells (PGCs) show global reduction in repressive epigenetic marks, and activation and repression of post-migratory PGC-specific genes involves DNA methylation and histone-arginine methylation. In post-migratory PGCs, epigenetic imprints that are specific to the parent of origin are erased. Subsequently, sex-specific imprints are established during male and female gametogenesis, and the de novo DNA methylation machinery has a central role in this process. DNA methylation is important for silencing retrotransposons in germ cells and therefore contributes to the maintenance of genomic integrity. Recent studies have revealed a link between DNA methylation and small-RNA-mediated silencing mechanisms. A number of histone methyltransferases are essential for establishing a chromosome structure that is appropriate for events that occur during meiosis and for activation and repression of genes that are necessary or unnecessary for meiosis. Meiotic sex-chromosome inactivation in male germ cells involves histone variants and epigenetic modifications. Global nuclear remodelling including histone–protamine exchange occurs in haploid spermatids. Expression of some haploid-specific genes relies on histone demethylation. A better understanding of the epigenetic regulation of germ-cell development will be of great importance for improvement of reproductive engineering technologies and human health. The epigenetic profile of germ cells undergoes several significant changes that are essential for post-fertilization development to occur. An emerging theme from recent studies is that epigenetic modifiers also have key roles in the development of germ cells themselves. The epigenetic profile of germ cells, which is defined by modifications of DNA and chromatin, changes dynamically during their development. Many of the changes are associated with the acquisition of the capacity to support post-fertilization development. Our knowledge of this aspect has greatly increased— for example, insights into how the re-establishment of parental imprints is regulated. In addition, an emerging theme from recent studies is that epigenetic modifiers have key roles in germ-cell development itself — for example, epigenetics contributes to the gene-expression programme that is required for germ-cell development, regulation of meiosis and genomic integrity. Understanding epigenetic regulation in germ cells has implications for reproductive engineering technologies and human health.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Animals / Biological and medical sciences / Biomedicine / Cancer Research / Cell Differentiation - genetics / Cell Differentiation - physiology / Cell differentiation, maturation, development, hematopoiesis / Cell physiology / Cells / Chromosomes / DNA methylation / Embryo, Mammalian / Embryonic Stem Cells - physiology / Epigenesis, Genetic - physiology / Epigenetic inheritance / Epigenetics / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Function / Genetic aspects / Genetics / Genomes / Germ cells / Germ Cells - physiology / Human Genetics / Humans / Mammals - genetics / Meiosis - genetics / Models, Biological / Molecular and cellular biology / Physiological aspects / Retroelements - genetics / review-article / RNA polymerase