Modern genetics of reproductive biology

Introduction “Epigenetics” has been described as the study of changes in gene expression that occur not due to changes in DNA sequence, but rather due to remodeling of the chromatin or modifications in DNA such as methylation, a process by which methyl groups are added to the base cytosine in DNA. Waddington defined “epigenetics” as “… the interactions of genes with their environment which bring the phenotype into being.” In those days, the gene as the unit of heritable material was a theoretical concept without a physical identity. Holliday and Pugh proposed that covalent chemical DNA modifications, including methylation of cytosine–guanine (CpG) dinucleotides, were the molecular mechanisms behind Waddington's hypothesis. Developmental processes are regulated largely by epigenetics, because different cell types maintain their fate during cell division even though their DNA sequences are essentially the same. The further revelations that X chromosome inactivation in mammals and genomic imprinting are regulated by epigenetic mechanisms highlighted the heritable nature of epigenetic gene-regulation mechanisms. The genomics revolution inspired the investigation of global, rather than local, gene analyses, and the term “epigenomics” was coined as the study of the “ … effects of chromatin structure, including the higher order of chromatin folding and attachment to the nuclear matrix, packaging of DNA around nucleosomes, covalent modifications of histone tails (acetylation, methylation, phosphorylation, ubiquitination), and DNA methylation”. The resistance of some gene loci to methylation reprogramming during embryogenesis revealed the possibility that epigenetic modifications are inherited not only during somatic-cell division, but also in subsequent generations.