Polymer coil\u2013globule phase transition is a universal folding principle of Drosophila epigenetic domains

Antony Lesage,Maria Barbi,Jean-Marc Victor,Vincent Dahirel

doi:10.1186/s13072-019-0269-6

Abstract

BackgroundLocalized functional domains within chromosomes, known as topologically associating domains (TADs), have been recently highlighted. In Drosophila, TADs are biochemically defined by epigenetic marks, this suggesting that the 3D arrangement may be the “missing link” between epigenetics and gene activity. Recent observations (Boettiger et al. in Nature 529(7586):418–422, 2016) provide access to structural features of these domains with unprecedented resolution thanks to super-resolution experiments. In particular, they give access to the distribution of the radii of gyration for domains of different linear length and associated with different transcriptional activity states: active, inactive or repressed. Intriguingly, the observed scaling laws lack consistent interpretation in polymer physics.ResultsWe develop a new methodology conceived to extract the best information from such super-resolution data by exploiting the whole distribution of gyration radii, and to place these experimental results on a theoretical framework. We show that the experimental data are compatible with the finite-size behavior of a self-attracting polymer. The same generic polymer model leads to quantitative differences between active, inactive and repressed domains. Active domains behave as pure polymer coils, while inactive and repressed domains both lie at the coil–globule crossover. For the first time, the “color-specificity” of both the persistence length and the mean interaction energy are estimated, leading to important differences between epigenetic states.ConclusionThese results point toward a crucial role of criticality to enhance the system responsivity, resulting in both energy transitions and structural rearrangements. We get strong indications that epigenetically induced changes in nucleosome–nucleosome interaction can cause chromatin to shift between different activity states.

Highlights

Chromosomes are giant polymers [1], i.e., very long chains of monomers
Theoretical framework of polymer physics We model an epigenetic domain as a polymer chain made of N identical monomers, of position ri, interacting by contacts with their nearest neighbors
Power‐law fit of experimental gyration radii leads to unusual exponents We used the full ensemble of measurements of Ref. [2] to analyze the scaling of the mean and median radii of gyration for Drosophila domains of different lengths and belonging to three epigenetic states: (i) active red types, covering the expressed regions, (ii) inactive black states and (iii) repressed blue domains, characterized by the presence of Polycomb-group (PcG) proteins

Summary

Introduction

Chromosomes are giant polymers [1], i.e., very long chains of monomers. In such systems, even very small interactions between monomers can strongly influence the whole structure, as many small interactions can add up to stabilize compact structures. Chromatin is known to be divided into compartments of various densities, including rather low-density regions, generally associated with transcribing genes, and more dense ones, more often silent or repressed from the transcription point of view. This spatial compartmentalization is achieved through linear segmentation of the genome into blocks or domains, with a biochemical. Recent observations (Boet‐ tiger et al in Nature 529(7586):418–422, 2016) provide access to structural features of these domains with unprece‐ dented resolution thanks to super-resolution experiments They give access to the distribution of the radii of gyration for domains of different linear length and associated with different transcriptional activity states: active, inactive or repressed. The observed scaling laws lack consistent interpretation in polymer physics

Results

Discussion

Conclusion