TADs are 3D structural units of higher-order chromosome organization in
            <i>Drosophila</i>

Szabo, Quentin; Jost, Daniel; Chang, Jia‐Ming; Cattoni, Diego I.; Papadopoulos, Giorgio L.; Bonev, Boyan; Sexton, Tom; Gurgo, Julian; Jacquier, Caroline; Nollmann, Marcelo; Bantignies, Frédéric; Cavalli, Giacomo

doi:10.1126/sciadv.aar8082

Cited by 256 publications

(307 citation statements)

References 44 publications

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“…This figure also illustrates different TAD hierarchies; the large TAD on the right, comprising an A compartment region, is further subdivided into minidomains (see Section and Figure ), whilst the large TAD on the left shows at least three levels of progressively larger domains, encompassing both A and B compartment regions. Hi‐C from Kc167 cells, A compartments from Kc167 cells, BEAF‐32 ChIP from Kc167 cells (ModENCODE GSM1535963), housekeeping genes from El‐Sharnouby et al and the FISH probe from Szabo et al ChIP, chromatin immunoprecipitation.…”

Section: Recent Experimental Results From Drosophila Give Fresh Insightmentioning

confidence: 99%

“…As mentioned above in the context of polytene chromosome bands, the visualization of chromatin organization provides a powerful complement to the genomic approaches to 3D architecture. Recently, super‐resolution microscopy has been used in combination with in situ fluorescent hybridization to image the organization of specific genome regions in Drosophila interphase cells . The images reveal a series of discrete 3D nanocompartments that correspond with B compartment TADs ( Figure a,b).…”

Section: Recent Experimental Results From Drosophila Give Fresh Insightmentioning

confidence: 99%

“…d) A compartment probe (from region indicated by red bar in Figure ) shows a more extended configuration, consistent with a series of minidomains. Reproduced with permission . Copyright 2018, American Association for the Advancement of Science.…”

Section: Recent Experimental Results From Drosophila Give Fresh Insightmentioning

confidence: 99%

“…Exploration of chromatin architecture in other taxa will help to determine to what extent principles of genome architecture are conserved (or not) throughout metazoans and beyond. How the 3D organization derived from population‐based genomic proximity mapping approaches relates to structures present in single cells at any one time is important to clarify. Imaging approaches will be vital for this and the recent applications of electron microscopy tomography and super‐resolution microscopy to chromatin structure provide promising approaches. For example, a recent study used an array of oligonucleotide probes in DNA‐fluorescence in situ hybridization (DNA‐FISH) to trace the nanoscale DNA architecture at the bithorax complex in single cells in Drosophila embryos .…”

Section: Discussionmentioning

confidence: 99%

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Chromatin Architecture in the Fly: Living without CTCF/Cohesin Loop Extrusion?

Matthews

White

2019

BioEssays

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The organization of the genome into topologically associated domains (TADs) appears to be a fundamental process occurring across a wide range of eukaryote organisms, and it likely plays an important role in providing an architectural foundation for gene regulation. Initial studies emphasized the remarkable parallels between TAD organization in organisms as diverse as Drosophila and mammals. However, whereas CCCTC‐binding factor (CTCF)/cohesin loop extrusion is emerging as a key mechanism for the formation of mammalian topological domains, the genome organization in Drosophila appears to depend primarily on the partitioning of chromatin state domains. Recent work suggesting a fundamental conserved role of chromatin state in building domain architecture is discussed and insights into genome organization from recent studies in Drosophila are considered.

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Section: Recent Experimental Results From Drosophila Give Fresh Insightmentioning

confidence: 99%

Section: Recent Experimental Results From Drosophila Give Fresh Insightmentioning

confidence: 99%

Section: Recent Experimental Results From Drosophila Give Fresh Insightmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Chromatin Architecture in the Fly: Living without CTCF/Cohesin Loop Extrusion?

Matthews

White

2019

BioEssays

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“…This work supported the role of epigenetic modifications in shaping the 3D structure of the distinct chromatin domains with different biochemical properties. More recently, using a combination of Hi‐C, 3D FISH labeling and super‐resolution imaging, consistent TAD‐based physical compartmentalization of chromatin was observed in Drosophila cell . Multiplexed super‐resolution FISH imaging was used for high‐resolution chromatin tracing of multiple regions of a chromosome, which starts to reveal TADs‐like structure at single cells .…”

Section: Visualizing Spatial Epigenomics Using Super‐resolution Micromentioning

confidence: 91%

A guide to visualizing the spatial epigenome with super‐resolution microscopy

Liu

2019

The FEBS Journal

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Genomic DNA in eukaryotic cells is tightly compacted with histone proteins into nucleosomes, which are further packaged into the higher‐order chromatin structure. The physical structuring of chromatin is highly dynamic and regulated by a large number of epigenetic modifications in response to various environmental exposures, both in normal development and pathological processes such as aging and cancer. Higher‐order chromatin structure has been indirectly inferred by conventional bulk biochemical assays on cell populations, which do not allow direct visualization of the spatial information of epigenomics (referred to as spatial epigenomics). With recent advances in super‐resolution microscopy, the higher‐order chromatin structure can now be visualized in vivo at an unprecedent resolution. This opens up new opportunities to study physical compaction of 3D chromatin structure in single cells, maintaining a well‐preserved spatial context of tissue microenvironment. This review discusses the recent application of super‐resolution fluorescence microscopy to investigate the higher‐order chromatin structure of different epigenomic states. We also envision the synergistic integration of super‐resolution microscopy and high‐throughput genomic technologies for the analysis of spatial epigenomics to fully understand the genome function in normal biological processes and diseases.

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How chromosome topologies get their shape: views from proximity ligation and microscopy methods

2020

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The 3D organization of our genome is an important determinant for the transcriptional output of a gene in (patho)physiological contexts. The spatial organization of linear chromosomes within nucleus is dominantly inferred using two distinct approaches, chromosome conformation capture (3C) and DNA fluorescent in situ hybridization (DNA–FISH). While 3C and its derivatives score genomic interaction frequencies based on proximity ligation events, DNA–FISH methods measure physical distances between genomic loci. Despite these approaches probe different characteristics of chromosomal topologies, they provide a coherent picture of how chromosomes are organized in higher‐order structures encompassing chromosome territories, compartments, and topologically associating domains. Yet, at the finer topological level of promoter–enhancer communication, the imaging‐centered and the 3C methods give more divergent and sometimes seemingly paradoxical results. Here, we compare and contrast observations made applying visual DNA–FISH and molecular 3C approaches. We emphasize that the 3C approach, due to its inherently competitive ligation step, measures only ‘relative’ proximities. A 3C interaction enriched between loci, therefore does not necessarily translates into a decrease in absolute spatial distance. Hence, we advocate caution when modeling chromosome conformations.

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TADs are 3D structural units of higher-order chromosome organization in Drosophila

Abstract: Drosophila chromosomes are organized in a series of nanocompartments that correspond to topologically associating domains.

Cited by 256 publications

References 44 publications

Chromatin Architecture in the Fly: Living without CTCF/Cohesin Loop Extrusion?

Chromatin Architecture in the Fly: Living without CTCF/Cohesin Loop Extrusion?

A guide to visualizing the spatial epigenome with super‐resolution microscopy

How chromosome topologies get their shape: views from proximity ligation and microscopy methods

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