From single genes to entire genomes: the search for a function of nuclear organization

Pueschel, Ringo; Coraggio, F; Meister, Peter

doi:10.1242/dev.129007

Cited by 41 publications

(39 citation statements)

References 125 publications

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“…Schreiner et al 2015) with high-throughput techniques such as chromosome conformation capture and its variants, in which chromatin structure can be reconstructed by sequencing and mapping physically adjacent regions of DNA. Although chromosome conformation capture has the limitation of operating at the scale of millions of cells, and averages out subtle differences between individual cells, it has demonstrated clear and reproducible differences between cell types (Pueschel et al 2016). Extending chromatin capture based approaches to single cell genomic analysis is unlikely to work robustly due to the low genome coverage per cell, but single cell analysis is developing fast for both transcriptional and epigenomic studies (Trapnell 2015).…”

Section: Discussionmentioning

confidence: 99%

Nuclear morphologies: their diversity and functional relevance

2016

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Studies of chromosome and genome biology often focus on condensed chromatin in the form of chromosomes and neglect the non-dividing cells. Even when interphase nuclei are considered, they are often then treated as interchangeable round objects. However, different cell types can have very different nuclear shapes, and these shapes have impacts on cellular function; indeed, many pathologies are linked with alterations to nuclear shape. In this review, we describe some of the nuclear morphologies beyond the spherical and ovoid. Many of the leukocytes of the immune system have lobed nuclei, which aid their flexibility and migration; smooth muscle cells have a spindle shaped nucleus, which must deform during muscle contractions; spermatozoa have highly condensed nuclei which adopt varied shapes, potentially associated with swimming efficiency. Nuclei are not passive passengers within the cell. There are clear effects of nuclear shape on the transcriptional activity of the cell. Recent work has shown that regulation of gene expression can be influenced by nuclear morphology, and that cells can drastically remodel their chromatin during differentiation. The link between the nucleoskeleton and the cytoskeleton at the nuclear envelope provides a mechanism for transmission of mechanical forces into the nucleus, directly affecting chromatin compaction and organisation.

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Section: Discussionmentioning

confidence: 99%

Nuclear morphologies: their diversity and functional relevance

2016

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“…We next searched for other genomic features that might explain the variations of sister locus separation. To detect potential implications of the chromatin state, we tested whether the degree of sister locus splitting correlates with nuclear positioning, as transcriptionally inactive constitutive heterochromatin localizes to the nuclear periphery, whereas actively transcribed euchromatin predominantly localizes to interior regions of the nucleus (Pueschel et al, 2016). We determined the distances of labelled loci from the nuclear boundary for each of the 16 cell lines (Fig.…”

Section: Degree Of Sister Locus Separation Correlates With Nuclear Pomentioning

confidence: 99%

Dynamics of sister chromatid resolution during cell cycle progression

Stanyte

Nuebler

Blaukopf

et al. 2018

Preprint

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Faithful genome transmission in dividing cells requires that the two copies of each chromosome's DNA package into separate, but physically linked, sister chromatids. The linkage between sister chromatids is mediated by cohesin, yet where sister chromatids are linked and how they resolve during cell cycle progression has remained unclear. Here, we investigated sister chromatid organization in live human cells using dCas9-mEGFP labelling of endogenous genomic loci. We detected substantial sister locus separation during G2 phase, irrespective of the proximity to cohesin enrichment sites. Almost all sister loci separated within a few hours after their respective replication, and then rapidly equilibrated their average distances within dynamic chromatin polymers. Our findings explain why the topology of sister chromatid resolution in G2 largely reflects the DNA replication program. Further, these data suggest that cohesin enrichment sites are not persistent cohesive sites in human cells. Rather, cohesion might occur at variable genomic positions within the cell population.

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“…In its pioneering work, almost a century ago, Emil Heitz introduced the terms of “euchromatin” and “heterochromatin” to account for the observed large-scale spatial density fluctuations of nucleus composition during interphase: as opposed to euchromatin, heterochromatin was referred to the chromosome “material” that remains densely stained during interphase (Brown 1966; Frenster et al 1963; Pueschel et al 2016). Further progresses in microscopy and immuno-staining/labeling techniques confirmed that euchromatic and heterochromatic compartments correspond actually to the aggregation of specialized functional chromatin: euchromatin is gene rich, displays higher expression level, and is generally more accessible and enriched for histone marks specific for active genes.…”

Section: Introduction: a Multiscale Compartmentalization Of The Genomementioning

confidence: 99%

Perspectives: using polymer modeling to understand the formation and function of nuclear compartments

2017

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Compartmentalization is a ubiquitous feature of cellular function. In the nucleus, early observations revealed a non-random spatial organization of the genome with a large-scale segregation between transcriptionally active—euchromatin—and silenced—heterochromatin—parts of the genome. Recent advances in genome-wide mapping and imaging techniques have strikingly improved the resolution at which nuclear genome folding can be analyzed and have revealed a multiscale spatial compartmentalization with increasing evidences that such compartment may indeed result from and participate to genome function. Understanding the underlying mechanisms of genome folding and in particular the link to gene regulation requires a cross-disciplinary approach that combines the new high-resolution techniques with computational modeling of chromatin and chromosomes. In this perspective article, we first present how the copolymer theoretical framework can account for the genome compartmentalization. We then suggest, in a second part, that compartments may act as a “nanoreactor,” increasing the robustness of either activation or repression by enhancing the local concentration of regulators. We conclude with the need to develop a new framework, namely the “living chromatin” model that will allow to explicitly investigate the coupling between spatial compartmentalization and gene regulation.

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From single genes to entire genomes: the search for a function of nuclear organization

Cited by 41 publications

References 125 publications

Nuclear morphologies: their diversity and functional relevance

Nuclear morphologies: their diversity and functional relevance

Dynamics of sister chromatid resolution during cell cycle progression

Perspectives: using polymer modeling to understand the formation and function of nuclear compartments

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