Super-resolution imaging reveals distinct chromatin folding for different epigenetic states

By Alistair N. Boettiger, Bogdan Bintu, Jeffrey R. Moffitt, Siyuan S Wang, Brian J. Beliveau, Geoffrey Fudenberg, Maxim Imakaev, Leonid A. Mirny, Chao-ting Wu, X. Zhuang. Nature, 2016

801 citations recorded by the source corpus.

Metazoan genomes are spatially organized at multiple scales, from packaging of DNA around individual nucleosomes to segregation of whole chromosomes into distinct territories. At the intermediate scale of kilobases to megabases, which encompasses the sizes of genes, gene clusters and regulatory domains, the three-dimensional (3D) organization of DNA is implicated in multiple gene regulatory mechanisms, but understanding this organization remains a challenge. At this scale, the genome is partitioned into domains of different epigenetic states that are essential for regulating gene expression. Here we investigate the 3D organization of chromatin in different epigenetic states using super-resolution imaging. We classified genomic domains in Drosophila cells into transcriptionally active, inactive or Polycomb-repressed states, and observed distinct chromatin organizations for each state. All three types of chromatin domains exhibit power-law scaling between their physical sizes in 3D and their domain lengths, but each type has a distinct scaling exponent. Polycomb-repressed domains show the densest packing and most intriguing chromatin folding behaviour, in which chromatin packing density increases with domain length. Distinct from the self-similar organization displayed by transcriptionally active and inactive chromatin, the Polycomb-repressed domains are characterized by a high degree of chromatin intermixing within the domain. Moreover, compared to inactive domains, Polycomb-repressed domains spatially exclude neighbouring active chromatin to a much stronger degree. Computational modelling and knockdown experiments suggest that reversible chromatin interactions mediated by Polycomb-group proteins play an important role in these unique packaging properties of the repressed chromatin. Taken together, our super-resolution images reveal distinct chromatin packaging for different epigenetic states at the kilobase-to-megabase scale, a length scale that is directly relevant to genome regulation.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/69dcff8c2ebed8bead49955a734f4cdb042ae9d4

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Citations in the corpus

Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. (2017, positive): “MLL2 is responsible for H3K4 trimethylation at bivalent promoters in ESCs (Figure 2B) (Denissov et al., 2014), whereas MLL1 is required for H3K4 trimethylation at only a small subset of genes, including HOX genes, emphasizing the non-redundant function of these two histone methyltransferases.”
Deep learning massively accelerates super-resolution localization microscopy (2018, background): “This will facilitate super-resolution studies of rare events, cellular heterogeneity, and of partly stochastic structures such as cytoskeletal polymers or chromosomes, whose characterization requires statistics on many configurations 37,38 .”
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Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells (2018, background): “Recent super-resolution imaging studies provide partial support for this view by showing repressed chromatin domains as spatially segregated compact structures or nanocompartments in single cells (16, 17).”
Chromatin organization by an interplay of loop extrusion and compartmental segregation (2017, background): “As high-resolution (7, 67, 68) and live-cell (69–71) imaging of chromatin is making dramatic progress, such questions may be addressed in the near future.”