Genetics alone cannot explain human variation and disease. Humans with the same
DNA sequence, such as monozygotic twins, and cloned animals frequently present
different phenotypes and degrees of sickness penetrance. The increasingly popular
term epigenetics embodies a partial explanation of both phenomena. First introduced
by C.H. Waddington in 1939 to name “the causal interactions between genes and
their products, which bring the phenotype into being,” it was subsequently defined as
those heritable changes in gene expression that are not due to any alteration in DNA
sequence. The best-known epigenetic marker is DNA methylation. From the initial
characterization of global hypomethylation of human tumors and the first hypermethylated
tumor suppressor, to the DNA methylation silencing of microRNAs, the
ongoing human epigenome projects, and the clinical approval of therapies with DNA
demethylating agents and histone deacetylase inhibitors, epigenetics has seized the
attention of biomedical researchers. The scenario is further enriched because DNA
methylation occurs in a highly complex chromatin network mediated by histone
modifications, which are also disrupted in human diseases. Aberrant epigenetic patterns
go beyond oncology to touch a wide range of fields of biomedical (immunology,
neurology, metabolism, imprinting, cardiovascular, etc.), scientific (machineries
for transcriptional activation and repression, high-order organization of DNA, etc.),
and industrial (animal and yeast models, agriculture, nutrition) knowledge that have
an impact on our lives.