Histone Variants and Reprogramming in Early Development

In addition to the well-studied epigenetic mechanisms associated with DNA methylation and histone modifications, histone variants have emerged as major regulators of chromatin activity. Apart from the major core histones, whose synthesis and incorporation into chromatin is linked to the S-phase of the cell cycle, histone ʻvariantsʼ are synthesised and incorporated into chromatin independently of DNA synthesis. These replacement histones confer distinct properties to nucleosomes and appear to be involved in important epigenetic processes. A significant role for histone variants in specialised chromatin signatures after fertilisation has emerged in the recent years. Here we review our knowledge on the involvement and the function of histone variants during the reprogramming phase occurring after mammalian fertilisation in vivo. We postulate that addressing the reprogramming mechanisms in its natural context, where this process occurs with a high efficiency to give rise to a new developmental programme, will help us to understand how we can modulate cell plasticity in induced and experimental models. Although there is still much to learn on how specific histone variants regulate reprogramming mechanistically, histone variants provide a remarkably versatile and exquisitely powerful way of regulating chromatin function in different biological contexts. Thus, the usage of histone variants provides an extra layer of regulation to the complexity of the reprogramming process.