Mechanisms and Functions of Chromosome Compartmentalization

Hildebrand, Erica; Dekker, Job

doi:10.1016/j.tibs.2020.01.002

Cited by 212 publications

(199 citation statements)

References 79 publications

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“…Such an assessment is distinctly simpler than the comparison against full image data. Considering that microphase separation has been proposed as a mechanism for the organization of different chromatin types and chromatin in general (3,(31)(32)(33)(34)(35), such a testing approach that is based in concrete experimental data seems relevant.…”

Section: Discussionmentioning

confidence: 99%

“…Another striking observation is that, across all investigated length scales, this packing follows an apparent hierarchical organization. Specifically, light and electron microscopy, and more recently biochemical methods in combination with modern DNA sequencing technology, have revealed how small domains of chromatin come together to form larger domains, which in turn come together to form yet bigger domains, and so forth (1)(2)(3). Microscopy approaches have shown hierarchical organization in the chromatin fibre at ≈ 10 nm (4,5), amongst chromatin domains at at the scale of ≈ 100 nm (6)(7)(8)(9), and also for compartments and territories on the micrometer scale (10).…”

Section: Introductionmentioning

confidence: 99%

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The domain-within-domain packing of euchromatin can be described as multiplicative cascades

Noa

Kuan

Aschmann

et al. 2020

Preprint

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The genome is packed into the cell nucleus in the form of chromatin. Biochemical approaches have revealed that chromatin is packed within domains, which group into larger domains, and so forth. Such domain-within-domain packing, also called hierarchical packing, is equally visible in super-resolution microscopy images of large-scale chromatin organization. While previous work has suggested that chromatin is partitioned into distinct domains via microphase separation, it is unclear how these domains organize into a hierarchical packing. A particular challenge is to find an image analysis approach that fully incorporates such hierarchical packing, so that hypothetical governing mechanisms of euchromatin packing can be compared against the results of such an analysis. Here, we obtain 3D STED super-resolution images from pluripotent zebrafish embryos labeled with improved DNA fluorescence stains, and demonstrate how the hierarchical packing of euchromatin in these images can be described as multiplicative cascades. Multiplicative cascades are an established theoretical concept to describe the placement of ever-smaller structures within bigger structures. Importantly, these cascades can generate artificial image data by applying a single rule again and again, and can be fully specified using only four parameters. Here, we show how the typical patterns of euchromatin organization are reflected in the values of these four parameters. In particular, we can pinpoint the values required to mimic a microphase-separated configuration of euchromatin. We suspect that the concept of multiplicative cascades can also be applied to images of other types of chromatin. In particular, cascade parameters could serve as test quantities to assess whether microphase separation or other theoretical models accurately reproduce the hierarchical packing of chromatin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The domain-within-domain packing of euchromatin can be described as multiplicative cascades

Noa

Kuan

Aschmann

et al. 2020

Preprint

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“…Across metazoans, individual chromosomes occupy discrete territories within the nucleus, and can be further separated into compartments that differ in transcriptional activity. The more active "A" compartments are gene-rich and more accessible, whereas the less active "B" compartments bear hallmarks of heterochromatin such as histone H3K9 and H3K27 methylation [reviewed in Hildebrand and Dekker (2020); Figure 1). Spatial organization, including association ARID4A (55, 52)…”

Section: Chromo Domain Proteins and Spatial Organization Of The Genomementioning

confidence: 99%

“…The combined application of high-resolution microscopy and genome-wide sequencing approaches now provides a comprehensive view of the organization of the genome into more transcriptionally active and accessible regions of euchromatin or less active and more compact regions of heterochromatin. These chromatin states are characterized by different patterns of histone modifications and spatial separation within the nucleus [reviewed in Hildebrand and Dekker (2020)]. Understanding the interplay between the histone modification landscape and the three-dimensional conformation of the genome will provide insight into the establishment and maintenance of cell type-specific gene expression programs.…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles for Chromo Domain Proteins in Genome Organization and Cell Fate in C. elegans

DasGupta

Lee

et al. 2020

Front. Cell Dev. Biol.

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In most eukaryotes, the genome is packaged with histones and other proteins to form chromatin. One of the major mechanisms for chromatin regulation is through post-translational modification of histone proteins. Recognition of these modifications by effector proteins, often dubbed histone "readers," provides a link between the chromatin landscape and gene regulation. The diversity of histone reader proteins for each modification provides an added layer of regulatory complexity. In this review, we will focus on the roles of chromatin organization modifier (chromo) domain containing proteins in the model nematode, Caenorhabditis elegans. An amenability to genetic and cell biological approaches, well-studied development and a short life cycle make C. elegans a powerful system to investigate the diversity of chromo domain protein functions in metazoans. We will highlight recent insights into the roles of chromo domain proteins in the regulation of heterochromatin and the spatial conformation of the genome as well as their functions in cell fate, fertility, small RNA pathways and transgenerational epigenetic inheritance. The spectrum of different chromatin readers may represent a layer of regulation that integrates chromatin landscape, genome organization and gene expression.

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“…Higher-order chromosome architecture allows cells to organize and maneuver large sections of chromatin to modulate gene expression, support DNA metabolism, and enable chromosome segregation (Bickmore andvan Steensel, 2013, Hildebrand andDekker, 2020). The structural compartmentalization of chromosomes also plays a key role during meiotic recombination (Zickler and Kleckner, 2015).…”

Section: Introductionmentioning

confidence: 99%

DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes

Markowitz

Heldrich

Hochwagen

2020

Preprint

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Meiotic chromosome pairing, recombination, and fertility depends on the conserved loop-axis architecture of meiotic chromosomes. This architecture is modulated by condensin, a structural maintenance of chromosome (SMC) complex that catalyzes chromatin loop formation. Here, we investigated how condensin is recruited to meiotic chromosomes in Saccharomyces cerevisiae. We show that double-strand-break (DSB) formation, the initiating event of meiotic recombination, causes condensin redistribution from the nucleolus to DSB hotspots, pericentromeric regions, and axis attachment sites. Hotspot association of condensin correlates weakly with break probability but does not depend on local DSB formation, whereas association with axis sites and pericentromeric regions depends on the Scc2-associated pool of cohesin, another SMC complex. Intriguingly, Scc2 distribution also changes in response to DSB formation. As condensin and Scc2-cohesin both catalyze chromatin loop extrusion, their redistribution upon DSB formation implies a profound change in chromatin loop dynamics that may help promote proper chromosome pairing and DNA repair.

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Mechanisms and Functions of Chromosome Compartmentalization

Cited by 212 publications

References 79 publications

The domain-within-domain packing of euchromatin can be described as multiplicative cascades

The domain-within-domain packing of euchromatin can be described as multiplicative cascades

Emerging Roles for Chromo Domain Proteins in Genome Organization and Cell Fate in C. elegans

DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes

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