Histone-based epigenetic information inheritance at the DNA replication fork

<p indent="0mm">In eukaryotes, histone modifications serve as one of the primary carriers of epigenetic information, shaping the chromatin landscape and regulating genome expression, which is fundamental for cellular function. During mitosis, daughter cells must inherit the epigenetic landscape of the parent cell to maintain cellular identity. DNA replication-coupled nucleosome assembly is a critical step in this process. During this process, parental histones are disassembled ahead of the replication fork and reassembled onto the newly synthesized daughter strands, facilitating the transmission of epigenetic information. Thus, the disassembly and recycling of parental histones ahead of the replication fork, as well as their transfer through the fork and reassembly onto the daughter strands, constitute the core steps for the inheritance of histone-carried epigenetic information by daughter cells. In light of recent advances in understanding parental histone recycling, this review highlights the mechanisms underlying parental histone inheritance. It provides an overview of the historical research and recent progress in this field, focusing on the fate of parental histones during DNA replication, their recycling onto nascent DNA strands, and their balanced distribution between the leading and lagging strands. In light of recent progress, this review highlights the collaborative capture of disassembled parental histones by the histone chaperone FACT at the replication fork and components of the replisome (primarily including the fork protection complex and the Mcm2 subunit of the replicative helicase). It elucidates the molecular mechanisms by which these histones are allocated and delivered to the two daughter strands. Based on this, we propose the concept of a “shuttle chaperone-histones-guiding chaperone” unit as a functional module for parental histone recycling, ensuring the effective inheritance of parental epigenetic information. Additionally, we discuss the mechanisms of epigenetic information inheritance carried by histones H3-H4 and H2A-H2B, focusing on the hexameric structural unit ((H3-H4)₂-(H2A-H2B)) captured by the endogenous replisome.