The roles of symmetric and asymmetric parental histone recycling in cell fate, development, and disease

Abstract

Replication of the epigenome occurs concurrently with DNA replication. A major component of epigenetic memory is contained in histones, and this memory is preserved via recycling of parental histones onto the leading and lagging strands of the replication fork. The histones of one parental strand must be incorporated into two nascent strands, a process governed by the replisome's histone chaperones. These chaperones determine which strand each histone is incorporated into and the frequency with which each strand receives parental histones, a determination that is essential for preserving epigenetic landscapes and ensuring proper gene expression following DNA replication. Here, we describe recent developments in our understanding of how parental histone recycling occurs and the effects it has on cells in developmental contexts. Although histones are generally recycled symmetrically to the leading and lagging strands, asymmetric histone recycling can occur naturally in some asymmetrically dividing cells or be induced by manipulating replisome components. Asymmetric histone recycling generates distinct epigenetic states at a given genomic locus, which can result in differential gene expression and ultimately different cell fates following cell division in multicellular organisms. This is important for future studies examining the role of epigenetics in both development and disease contexts.