Dataset Information

Bottom-up modeling of chromatin segregation due to epigenetic modifications.

ABSTRACT: 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.

SUBMITTER: MacPherson Q

PROVIDER: S-EPMC6294944 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Bottom-up modeling of chromatin segregation due to epigenetic modifications.

MacPherson Quinn Q Beltran Bruno B Spakowitz Andrew J AJ

Proceedings of the National Academy of Sciences of the United States of America 20181126 50

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 t ...[more]

PMID: 30478042

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Project description:Polyphonic music listening well exemplifies processes typically involved in daily auditory scene analysis situations, relying on an interactive interplay between bottom-up and top-down processes. Most studies investigating scene analysis have used elementary auditory scenes, however real-world scene analysis is far more complex. In particular, music, contrary to most other natural auditory scenes, can be perceived by either integrating or, under attentive control, segregating sound streams, often carried by different instruments. One of the prominent bottom-up cues contributing to multi-instrument music perception is their timbre difference. In this work, we introduce and validate a novel paradigm designed to investigate, within naturalistic musical auditory scenes, attentive modulation as well as its interaction with bottom-up processes. Two psychophysical experiments are described, employing custom-composed two-voice polyphonic music pieces within a framework implementing a behavioral performance metric to validate listener instructions requiring either integration or segregation of scene elements. In Experiment 1, the listeners' locus of attention was switched between individual instruments or the aggregate (i.e., both instruments together), via a task requiring the detection of temporal modulations (i.e., triplets) incorporated within or across instruments. Subjects responded post-stimulus whether triplets were present in the to-be-attended instrument(s). Experiment 2 introduced the bottom-up manipulation by adding a three-level morphing of instrument timbre distance to the attentional framework. The task was designed to be used within neuroimaging paradigms; Experiment 2 was additionally validated behaviorally in the functional Magnetic Resonance Imaging (fMRI) environment. Experiment 1 subjects (N = 29, non-musicians) completed the task at high levels of accuracy, showing no group differences between any experimental conditions. Nineteen listeners also participated in Experiment 2, showing a main effect of instrument timbre distance, even though within attention-condition timbre-distance contrasts did not demonstrate any timbre effect. Correlation of overall scores with morph-distance effects, computed by subtracting the largest from the smallest timbre distance scores, showed an influence of general task difficulty on the timbre distance effect. Comparison of laboratory and fMRI data showed scanner noise had no adverse effect on task performance. These Experimental paradigms enable to study both bottom-up and top-down contributions to auditory stream segregation and integration within psychophysical and neuroimaging experiments.

Dataset Information

Bottom-up modeling of chromatin segregation due to epigenetic modifications.

Publications

Bottom-up modeling of chromatin segregation due to epigenetic modifications.

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