Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions

Cattoni, Diego I.; Gizzi, Andrés M. Cardozo; Georgieva, Mariya; Stefano, Marco Di; Valeri, Alessandro; Chamousset, Delphine; Houbron, Christophe; Déjardin, Stéphanie; Fiche, Jean-Bernard; González, Inma; Chang, Jia‐Ming; Sexton, Tom; Martí‐Renom, Marc A.; Bantignies, Frédéric; Cavalli, Giacomo; Nöllmann, Marcelo

doi:10.1038/s41467-017-01962-x

Cited by 146 publications

(118 citation statements)

References 62 publications

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“…Previous studies have reported that loci which display strong interactions in Hi-C do 201 not always equate to frequent interactions in single cells (Bonev et al, 2017;202 Fudenberg and Imakaev, 2017). Therefore we wanted to accurately quantitate the 203 frequency of polycomb chromatin domain interactions by determining the number of 204 FISH probe measures that may be considered to be in contact (Cattoni et al, 2017). 205…”

Section: Polycomb Chromatin Domain Interactions Are Disrupted By Cohementioning

confidence: 99%

“…To assess what proportion of our inter-probe distance measurements might be considered as co-incident we applied the following rationale, which is as described (Cattoni et al, 2017). To measure the error in colocalisation precision within a realistic, non-ideal experimental situation, we labelled and hybridised the same fosmid probe with both digoxygenin (detected with FITC) and Cy3 in cells, as per the experimental conditions.…”

Section: Contact Probability Threshold Calculationmentioning

confidence: 99%

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Cohesin disrupts polycomb-dependent chromosome interactions

Rhodes

Feldmann

Hernández-Rodríguez

et al. 2019

Preprint

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16How chromosome organisation is related to genome function remains poorly 17 understood. Cohesin, loop-extrusion, and CTCF have been proposed to create 18 structures called topologically associating domains (TADs) to regulate gene 19 expression. Here, we examine chromosome conformation in embryonic stem cells 20 lacking cohesin and find as in other cell types that cohesin is required to create TADs 21 and regulate A/B compartmentalisation. However, in the absence of cohesin we 22 identify a series of long-range chromosomal interactions that persist. These 23 correspond to regions of the genome occupied by the polycomb repressive system, 24 depend on PRC1, and we discover that cohesin counteracts these interactions. This 25 disruptive activity is independent of CTCF and TADs, and regulates gene repression 26 by the polycomb system. Therefore, in contrast to the proposal that cohesin creates 27 structure in chromosomes, we discover a new role for cohesin in disrupting polycomb-28 dependent chromosome interactions to regulate gene expression. 29

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Section: Polycomb Chromatin Domain Interactions Are Disrupted By Cohementioning

confidence: 99%

Section: Contact Probability Threshold Calculationmentioning

confidence: 99%

Cohesin disrupts polycomb-dependent chromosome interactions

Rhodes

Feldmann

Hernández-Rodríguez

et al. 2019

Preprint

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“…This model would explain our observations that CTCF/cohesin sites flanking the α-globin self-interacting domain become juxtaposed around a decompacted loop of chromatin in erythroblasts. In this model, domains could arise from a dynamic balance of cohesin loading and removal and loop extrusion and blocking 26 . We have previously noted an accumulation of cohesin in erythroid cells around all five enhancer-like elements of the α-globin cluster 13 , which may act as entry points for cohesin.…”

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confidence: 99%

A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions

Brown

Roberts

Graham

et al. 2017

Preprint

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A variety of self-interacting domains, defined at different levels of resolution, have been described in mammalian genomes. These include Chromatin Compartments (A and B)1, Topologically Associated Domains (TADs)2,3, contact domains4,5, sub-TADs6, insulated neighbourhoods7 and frequently interacting regions (FIREs)8. Whereas many studies have found the organisation of self-interacting domains to be conserved across cell types389, some do form in a lineage-specific manner6710. However, it is not clear to what degree such tissue-specific structures result from processes related to gene activity such as enhancer-promoter interactions or whether they form earlier during lineage commitment and are therefore likely to be prerequisite for promoting gene expression. To examine these models of genome organisation in detail, we used a combination of high-resolution chromosome conformation capture, a newly-developed form of quantitative fluorescence in-situ hybridisation and super-resolution imaging to study a 70 kb self-interacting domain containing the mouse α-globin locus. To understand how this self-interacting domain is established, we studied the region when the genes are inactive and during erythroid differentiation when the genes are progressively switched on. In contrast to many current models of long-range gene regulation, we show that an erythroid-specific, decompacted self-interacting domain, delimited by convergent CTCF/cohesin binding sites, forms prior to the onset of robust gene expression. Using previously established mouse models we show that formation of the self-interacting domain does not rely on interactions between the α-globin genes and their enhancers. As there are also no tissue-specific changes in CTCF binding, then formation of the domain may simply depend on the presence of activated lineage-specific cis-elements driving a transcription-independent mechanism for opening chromatin throughout the 70 kb region to create a permissive environment for gene expression. These findings are consistent with a model of loop-extrusion in which all segments of chromatin, within a region delimited by CTCF boundary elements, can contact each other. Our findings suggest that activation of tissue-specific element(s)within such a self-interacting region is sufficient to influence all chromatin within the domain.

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“…Interestingly, the behavior of the two alleles in the same nucleus is not correlated, which suggests that the variability present is largely intrinsic and not dependent on cell-level variables such as cycle stage [16]. However, energy was not considered as a variable by the authors.…”

Section: Figurementioning

confidence: 96%

The Energy as a Determinant Factor in the Ethiopathogeny of Chromosomal Abnormalities. The Unsuspected Bioenergetic Role of Melanin

Herrera¹

2020

Chromosomal Abnormalities

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In the study of chromosomal abnormalities, in genetics, and in medicine in general, attention is rarely paid to the role of energy in the healthy subject and in the sick patient. The research on the chromosomal anomalies that are constantly published, does not mention the energy necessary for the biochemical processes involved in the function, replication and formation of genes, to be carried out in an adequate way. It seems that it is assumed that energy levels are always fine or at least did not have a significant role in the conditions associated with what we call chromosomal anomalies. A characteristic of the cell nucleus that has gone unnoticed is that it contains neither mitochondria nor ATP, much less glucose. Perhaps because of this, some researchers and clinicians come to think that the nucleus of cells does not require energy. The purpose of this work is to draw attention to the importance of energy levels in all the metabolic processes of the cell; and to make known that glucose is not an energy source, as it is only a source of carbon chains; and finally remark that our body, through melanin, can take energy directly from light.

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Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions

Cited by 146 publications

References 62 publications

Cohesin disrupts polycomb-dependent chromosome interactions

Cohesin disrupts polycomb-dependent chromosome interactions

A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions

The Energy as a Determinant Factor in the Ethiopathogeny of Chromosomal Abnormalities. The Unsuspected Bioenergetic Role of Melanin

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