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

Matthews, Nicholas E.; White, Robert A.

doi:10.1002/bies.201900048

Cited by 54 publications

(31 citation statements)

References 51 publications

(124 reference statements)

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“…In Drosophila , CTCF-binding sites also overlap cohesin ChIP-seq peaks 44 (Supplementary Fig. 7 ), but do not exhibit motif orientation bias at domain borders 45 and do not anchor Hi–C peaks 46 , 47 . This reinforces the notion that, while the conserved ZF domain is an impediment to cohesin translocation, the mammalian N terminus is required to fully retain cohesin and stabilize chromatin loops as they appear by Hi–C.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of CTCF binding polarity in genome folding

et al. 2020

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Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize loops, the molecular basis of this polarity remains unclear. By combining ChIP-seq and single molecule live imaging we report that CTCF positions cohesin, but does not control its overall binding dynamics on chromatin. Using an inducible complementation system, we find that CTCF mutants lacking the N-terminus cannot insulate TADs properly. Cohesin remains at CTCF sites in this mutant, albeit with reduced enrichment. Given the orientation of CTCF motifs presents the N-terminus towards cohesin as it translocates from the interior of TADs, these observations explain how the orientation of CTCF binding sites translates into genome folding patterns.

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Section: Discussionmentioning

confidence: 99%

Molecular basis of CTCF binding polarity in genome folding

et al. 2020

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“…2). К наиболее хорошо изученным C2H2-белкам относятся первый описанный у высших эукариот белок, обладающий инсуляторными свойствами, Su(Hw), и гомолог СTCF млекопитающих [22,24,169,170]. Оба инсуляторных белка обладают сходным строением -содержат концевые неструктурированные домены и расположенный в центре кластер из 11 (dСTCF) или 12 (Su(Hw)) C2H2-доменов.…”

Section: другие с2н2-белки позвоночных с архитектурными функциямиunclassified

CTCF As an Example of DNA-Binding Transcription Factors Containing Clusters of C2H2-Type Zinc Fingers

et al. 2021

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In mammals, most of the boundaries of topologically associating domains and all well-studied insulators are rich in binding sites for the CTCF protein. According to existing experimental data, CTCF is a key factor in the organization of the architecture of mammalian chromosomes. A characteristic feature of the CTCF is that the central part of the protein contains a cluster consisting of eleven domains of C2H2-type zinc fingers, five of which specifically bind to a long DNA sequence conserved in most animals. The class of transcription factors that carry a cluster of C2H2-type zinc fingers consisting of five or more domains (C2H2 proteins) is widely represented in all groups of animals. The functions of most C2H2 proteins still remain unknown. This review presents data on the structure and possible functions of these proteins, using the example of the vertebrate CTCF protein and several well- characterized C2H2 proteins in Drosophila and mammals.

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“…Extrusion has, however, several problems: (1) removal of cohesin and CTCF from chromosomes showed limited effects on steady-state transcription [ 85 , 86 , 87 ]; (2) extrusion does not appear to be a general phenomenon in chromatin domains; indeed, it is “malleable and variable between individual cells” [ 88 ] and absent in Drosophila [ 89 ] (in which case building of TADs does not appear to make use of the CTCF/cohesin loop extrusion mechanism) and in many other cases; for instance, the Hi-C approach can fail to detect known structures such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate [ 90 ]; (3) extrusion can take place not only through the classical two-sided manner but also through a one-sided manner raising another unsolved problem [ 91 ].…”

Section: Genome Sub-compartments and Isochoresmentioning

confidence: 99%

The “Genomic Code”: DNA Pervasively Moulds Chromatin Structures Leaving no Room for “Junk”

Bernardi

2021

Life

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The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin located peripherally. This bimodality was later confirmed and extended by the discoveries (1) of LADs, the Lamina-Associated Domains, and InterLADs; (2) of two “spatial compartments”, A and B, identified on the basis of chromatin interactions; and (3) of “forests and prairies” characterized by high and low CpG islands densities. Chromatin compartments were shown to be associated with the compositionally different, flat and single- or multi-peak DNA structures of the two, GC-poor and GC-rich, “super-families” of isochores. At the second, sub-compartment, level, chromatin corresponds to flat isochores and to isochore loops (due to compositional DNA gradients) that are susceptible to extrusion. Finally, at the short-sequence level, two sets of sequences, GC-poor and GC-rich, define two different nucleosome spacings, a short one and a long one. In conclusion, chromatin structures are moulded according to a “genomic code” by DNA sequences that pervade the genome and leave no room for “junk”.

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

Cited by 54 publications

References 51 publications

Molecular basis of CTCF binding polarity in genome folding

Molecular basis of CTCF binding polarity in genome folding

CTCF As an Example of DNA-Binding Transcription Factors Containing Clusters of C2H2-Type Zinc Fingers

The “Genomic Code”: DNA Pervasively Moulds Chromatin Structures Leaving no Room for “Junk”

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