Developmental epigenetic programming: chasing shadows

The ways in which epigenetic modifications fix the effects of early environmental events, ensuring sustained responses to transient stimuli, which result into modified gene expression patterns and phenotypes later in life, is a topic of considerable interest. Increasing numbers of genome-wide studies based on high-throughput technologies and focusing on humans and mice have revealed additional complexity in epigenetic processes, highlighting the importance of stage-, sex-, and cell-specific epigenetic landscapes, and of crosstalk between the different epigenetic marks. This paper focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, positions and functions of relevant epigenetic marks. Animal models, including mice, rats, sheep, pigs and rabbits, remain a vital tool for studying the influence of early nutritional events on adult health and disease. In recent months, a number of studies focusing on the Developmental Origin of Health and Disease (DOHaD) and metabolic programming have identified links between early nutrition, epigenetic processes, and long-term illness. They have demonstrated the existence of an on-going self-propagating epigenetic cycle, of metabolic memories and ageing processes. However most epigenetic studies have only addressed the long-term effects on a small number of epigenetic marks, at the global or individual gene level, of environmental stressors in humans and animal models. Despite recent progress, we are still far from understanding how, when and where environmental stressors disturb key epigenetic mechanisms. Thus identifying the original key marks and their changes throughout development, during an individual’s lifetime or over several generations, remains a challenging issue.