Abstract
BackgroundIn higher eukaryotes, the genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts. While a crumpled/fractal globule organization has received experimental supports at higher-order levels, the organization principles that govern chromatin dynamics within these TADs remain unclear. Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus-specific interaction takes place.ResultsHere, we use data from diverse 3C-derived methods to explore chromatin dynamics within mouse and Drosophila TADs. In mouse Embryonic Stem Cells (mESC), that possess large TADs (median size of 840 kb), we show that the statistical helix model, but not globule models, is relevant not only in gene-rich TADs, but also in gene-poor and gene-desert TADs. Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells. Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization. In Drosophila, which possesses TADs of smaller sizes (median size of 70 kb), we show that, while chromatin compaction and flexibility are finely tuned according to the epigenetic landscape, chromatin dynamics within TADs is generally compatible with an unconstrained polymer configuration.ConclusionsModels issued from polymer physics can accurately describe the organization principles governing chromatin dynamics in both mouse and Drosophila TADs. However, constraints applied on this dynamics within mammalian TADs have a peculiar impact resulting in a statistical helix organization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1786-8) contains supplementary material, which is available to authorized users.
Highlights
In higher eukaryotes, the genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts
Hi-C approaches provided genome-wide profiling of contact frequencies in the yeast (Saccharomyces cerevisiae) [5], fly (Drosophila melanogaster) [6], mouse (Mus musculus domesticus) [7] and human [8, 9] genomes. While these data confirmed that higher-order chromatin dynamics appears to be globally unconstrained in yeast, they showed that this organization level is constrained in higher eukaryotes where the chromatin is compartmentalized into chromosomal territories that are themselves further partitioned into the so-called “Topologically Associating Domains” (TADs) [10] or contact domains [9]
We focused on three types of domains: five gene-rich TADs, two genepoor TADs [19] and one gene-desert TAD (Additional file 1a and b)
Summary
The genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts. Hi-C approaches (that combine 3C assays with highthroughput sequencing) provided genome-wide profiling of contact frequencies in the yeast (Saccharomyces cerevisiae) [5], fly (Drosophila melanogaster) [6], mouse (Mus musculus domesticus) [7] and human [8, 9] genomes While these data confirmed that higher-order chromatin dynamics appears to be globally unconstrained in yeast, they showed that this organization level is constrained in higher eukaryotes where the chromatin is compartmentalized into chromosomal territories that are themselves further partitioned into the so-called “Topologically Associating Domains” (TADs) [10] or contact domains [9]. While the involvement of locus-specific factors in chromatin-loop formation, within TADs, is well established [9], the physical properties that govern the underlying chromatin dynamics at that scale remains unknown
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