The role of epigenetic inheritance in the maintenance or alteration of cellular identity

Abstract

Cell identity is tightly regulated by cell-specific expression patterns. This is caused by epigenetic factors that pack the DNA into chromatin, making it accessible or inaccessible to transcription machinery. The regulation of these epigenetic factors is poorly understood, especially how this epigenetic memory is transmitted to daughter cells after mitosis. Accurate transmission of expression patterns after cell division is essential for preserving proper cell lineages. As DNA replication disrupts the chromatin structure, there must be highly regulated mechanisms involved in the restoration of chromatin. However, these mechanisms remain unclear. In this review, an overview is given of the current finding and models present in the research field of epigenetic inheritance. The focus will be on histone posttranslational modifications (PTMs) as these epigenetic factors are key determinants that correlate with the chromatin state and transcriptional status. Recent studies showed that repressive PTMs are inherited by staying attached to recycled histones during DNA replication. Afterwards, positive read-write loops restore these PTMs on neighboring naïve histones. For activating PTMs more remains unclear as their attached histones are dispersed during DNA replication. Transcription initiation seems an important factor for the appropriate restoration of accessible chromatin, but furthermore the mechanisms involved remain hypothetical. PTMs are a barrier for reprogramming of cell fate as they are important factors in maintaining the cellular epigenetic memory. There are techniques that enable reprogramming of cell fate, but they have low success rates with limited possibilities. Understanding the mechanisms involved in PTM inheritance could be used to develop more efficient reprogramming techniques in the future, which will have many therapeutic benefits.