The dynamics of chromatin states mediated by epigenetic modifications during somatic cell reprogramming

Abstract

Somatic cell reprogramming (SCR) is the conversion of differentiated somatic cells into totipotent or pluripotent cells through a variety of methods. Somatic cell reprogramming also provides a platform to investigate the role of chromatin-based factors in establishing and maintaining totipotency or pluripotency, since high expression of totipotency- or pluripotency-related genes usually require an active chromatin state. Several studies in plants or mammals have recently shed light on the molecular mechanisms by which epigenetic modifications regulate the expression of totipotency or pluripotency genes by altering their chromatin states. In this review, we present a comprehensive overview of the dynamic changes in epigenetic modifications and chromatin states during reprogramming from somatic cells to totipotent or pluripotent cells. In addition, we illustrate the potential role of DNA methylation, histone modifications, histone variants, and chromatin remodeling during somatic cell reprogramming, which will pave the way to developing reliable strategies for efficient cellular reprogramming.

Keywords: cell pluripotency; cell totipotency; chromatin state; epigenetic modification; gene expression; somatic cell reprogramming.

FIGURE 1

An overview of epigenetic factors dynamically regulating the chromatin state during somatic cell reprogramming. The diagrams illustrate the reprogramming of somatic cells to pluripotent or totipotent cells along with the associated epigenetic modifications in plants (A) and mammals (B). DNA methylation acts as a barrier during SCR in both mammals and plants. Most pluripotency or totipotency genes are hypermethylated and transcriptionally silenced in somatic cells, and they are (re) activated through active DNA demethylation during SCR. Histone methylation is also required for SCR. Different histone methylation marks induce open or repressive chromatin states, ensuring the activation of pluripotency or totipotency genes to promote SCR. Histone acetylation acts as an epigenetic activator of reprogramming by establishing a chromatin structure that promotes the activation of a transcriptional network that regulates pluripotency or totipotency. Histone variants and chromatin remodeling are also associated with histone modifications and impose a repressive chromatin state to prevent the reactivation of critical pluripotency or totipotency genes during SCR.