ReviewGENETICS

Replicating nucleosomes

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Science Advances  07 Aug 2015:
Vol. 1, no. 7, e1500587
DOI: 10.1126/sciadv.1500587

Figures

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