Epigenetic Regulation of Male Germ Cell Differentiation

Abstract

Male germ cell differentiation is a complex developmental program that produces highly specialized mature spermatozoa capable of independent movement and fertilization of an egg. Germ cells are unique in their capability to generate new organisms, and extra caution has to be taken to secure the correct inheritance of genetic and epigenetic information. Male germ cells are epigenetically distinct from somatic cells and they undergo several important epigenetic transitions. In primordial germ cells (PGCs), epigenome is reprogrammed by genome-wide resetting of epigenetic marks, including the sex-specific imprinting of certain genes. Postnatal spermatogenesis is characterized by drastic chromatin rearrangements during meiotic recombination, sex chromosome silencing, and compaction of sperm nuclei, which is accomplished by replacing near to all histones by sperm-specific protamines. Small RNAs, including microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs) and PIWI-interacting RNAs (piRNAs) are also involved in the control of male gamete production. The activities of small RNAs in male germ cells are diverse, and include miRNA- and endo-siRNA-mediated posttranscriptional mRNA regulation and piRNA-driven transposon silencing and the control of DNA methylation in PGCs. In this chapter, we give a brief review on the epigenetic processes that govern chromatin organization and germline-specific gene expression in differentiating male germ cells.

Diversity and functional convergence of small noncoding RNAs in male germ cell differentiation and fertilization

“…Accumulating evidence suggest that sncRNAs play key regulatory roles in cell differentiation and development (Tang 2010;Meikar et al 2013). The presence and functional activity of some sncRNAs as piRNAs or endo-siRNAs were restricted to germline, but recent studies have also identified them in different somatic cell types (Akkouche et al 2013;Peng and Lin 2013;Juliano et al 2014), opening a new fascinating and unexpected dimension of their regulatory roles.…”

DNA methylation in spermatogenesis and male infertility

“…(26)(27)(28)(29)(30), predominantly methylates hemimethylated CpG dinucleotides in the genome, and is considered to be the key maintenance methyltransferase during cell division (29)(30)(31)(32)(33). The DNMT2 gene is the most highly conserved of the methyltransferases in eukaryotes, and has been identified in organisms that exhibit DNA methylation, as well as in those that do not (26)(27)(28)(29)(30). DNMT3a and DNMT3b primarily perform de novo methyl transfer reactions via interactions with transcriptional repressors.…”

Perspectives on mammalian chromatoid body research

“…Development of both male and female germ cells is controlled by unique gene expression programs. These programs involve genetic events and epigenetic reprogramming, such as histone modifications and DNA methylation (reviewed by Kota and Feil, 2010;Meikar et al, 2013). One of the most important genetic events that take place during gametogenesis is meiotic recombination provided by the crossover between paired regions of homologous chromosomes.…”