Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 50, Pages 12739-12744Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1812268115
Keywords
epigenetic regulation; genomic architecture; Hi-C; chromosomal organization; polymer simulation
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Funding
- National Science Foundation (NSF), Physics of Living Systems Program [PHY-1707751]
- NSF Graduate Fellowship program [DGE-1656518]
- NIH Training Grant [T32GM008294]
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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.
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