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Title: Bottom–up modeling of chromatin segregation due to epigenetic modifications
We use a chromosome-scale simulation to show that the preferential binding of heterochromatin protein 1 (HP1) to regions high in histone methylation (specifically H3K9me3) results in phase segregation and reproduces features of the observed Hi-C contact map. Specifically, we perform Monte Carlo simulations with one computational bead per nucleosome and an H3K9me3 pattern based on published ChIP-seq signals. We implement a binding model in which HP1 preferentially binds to trimethylated histone tails and then oligomerizes to bridge together nucleosomes. We observe a phase reminiscent of heterochromatin—dense and high in H3K9me3—and another reminiscent of euchromatin—less dense and lacking H3K9me3. This segregation results in a plaid contact probability map that matches the general shape and position of published Hi-C data. Analysis suggests that a roughly 20-kb segment of H3K9me3 enrichment is required to drive segregation into the heterochromatic phase.  more » « less
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Author(s) / Creator(s):
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Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Page Range / eLocation ID:
12739 to 12744
Medium: X
Sponsoring Org:
National Science Foundation
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