Replicating Nucleosomes - PubMed (original) (raw)

Replicating Nucleosomes

Srinivas Ramachandran et al. Sci Adv. 2015.

Abstract

Eukaryotic replication disrupts each nucleosome as the fork passes, followed by re-assembly of disrupted nucleosomes and incorporation of newly synthesized histones into nucleosomes in the daughter genomes. In this review, we examine this process of replication-coupled nucleosome assembly to understand how characteristic steady state nucleosome landscapes are attained. Recent studies have begun to elucidate mechanisms involved in histone transfer during replication and maturation of the nucleosome landscape after disruption by replication. A fuller understanding of replication-coupled nucleosome assembly will be needed to explain how epigenetic information is replicated at every cell division.

Keywords: epigenetics; histone modification; histone variants; replication-coupled nucleosome assembly.

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Figures

Fig. 1

Fig. 1. Distinct mechanisms of incorporation of H3.3 at active and silent regions of the genome.

At transcriptionally active regions, nucleosomes are disrupted by RNA polymerase or nucleosome remodelers, resulting in occasional nucleosome loss, with replacement by nucleosomes containing H3.3, which unlike H3 is present throughout the cell cycle. At regions of unusual base composition, which include telomeres, CpG islands, and short-period satellite repeats, the lack of nucleosome-stabilizing sequences results in relatively frequent nucleosome loss, with replacement by H3.3 nucleosomes.

Fig. 2

Fig. 2. Three models of propagating histone modifications through replication.

In the template-binding model (42), adjacent nucleosomes are modified by a histone-modifying enzyme that binds the modified residue on a nearby tail. In the constitutive model (47), H3K27 methylation is restored by recognition of H3A31 but not H3.3T31 by ATXR5/6, such that only replication-coupled (H3) nucleosomes, not replication-independent (H3.3) nucleosomes, are methylated on H3K27. In the bridging model (48), PRC1 bridges nucleosomes across daughter chromatids.

Fig. 3

Fig. 3. Different modes of inheritance of old H3 and newly synthesized H3 on newly replicated DNA.

Fig. 4

Fig. 4. Probability of faithful inheritance at various thresholds of old histone segregation.

Given that old (H3-H4)2 is segregated randomly to daughter chromosomes during replication, we can think of each nucleosome assembled as a Bernoulli trial, with the probability of a daughter chromosome assembling a nucleosome with old (H3-H4)2 the same as the probability of assembling a nucleosome with new (H3-H4)2, both of which would be 0.5. We can then ask, what is the probability that at least a given percentage of old (H3-H4)2 in a nucleosome array of a given size is obtained by a daughter chromosome? The x axis of this plot represents the different nucleosome array sizes. The y axis represents the probability of the daughter chromosome getting at least a given percentage of old (H3-H4)2. We define this binomial probability as the probability of faithful inheritance. The dashed gray line represents the minimum size of the nucleosome array that would ensure faithful inheritance of at least 33% of old (H3-H4)2.

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