scholarly journals Multi-Scale Organization of the Drosophila melanogaster Genome

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 817
Author(s):  
Samantha C. Peterson ◽  
Kaylah B. Samuelson ◽  
Stacey L. Hanlon

Interphase chromatin, despite its appearance, is a highly organized framework of loops and bends. Chromosomes are folded into topologically associating domains, or TADs, and each chromosome and its homolog occupy a distinct territory within the nucleus. In Drosophila, genome organization is exceptional because homologous chromosome pairing is in both germline and somatic tissues, which promote interhomolog interactions such as transvection that can affect gene expression in trans. In this review, we focus on what is known about genome organization in Drosophila and discuss it from TADs to territory. We start by examining intrachromosomal organization at the sub-chromosome level into TADs, followed by a comprehensive analysis of the known proteins that play a key role in TAD formation and boundary establishment. We then zoom out to examine interhomolog interactions such as pairing and transvection that are abundant in Drosophila but rare in other model systems. Finally, we discuss chromosome territories that form within the nucleus, resulting in a complete picture of the multi-scale organization of the Drosophila genome.

2021 ◽  
Author(s):  
Ivo Suter ◽  
Lukas Emmenegger ◽  
Dominik Brunner

<p>Reducing air pollution, which is the world's largest single environmental health risk, demands better-informed air quality policies. Consequently, multi-scale air quality models are being developed with the goal to resolve cities. One of the major challenges in such model systems is to accurately represent all large- and regional-scale processes that may critically determine the background concentration levels over a given city. This is particularly true for longer-lived species such as aerosols, for which background levels often dominate the concentration levels, even within the city. Furthermore, the heterogeneous local emissions, and complex dispersion in the city have to be considered carefully.</p><p>In this study, the impact of processes across a wide range of scales on background concentrations over Switzerland and the city of Zurich was modelled by performing one year of nested European and Swiss national COSMO-ART simulations to obtain adequate boundary conditions for gas-phase chemical, aerosol and meteorological conditions for city-resolving simulations. The regional climate chemistry model COSMO-ART (Vogel et al. 2009) was used in a 1-way coupled mode. The outer, European, domain, which was driven by chemical boundary conditions from the global MOZART model, had a 6.6 km horizontal resolution and the inner, Swiss, domain one of 2.2 km. For the city scale, a catalogue of more than 1000 mesoscale flow patterns with 100 m resolution was created with the model GRAMM, based on a discrete set of atmospheric stabilities, wind speeds and directions, accounting for the influence of land-use and topography. Finally, the flow around buildings was solved with the CFD model GRAL forced at the boundaries by GRAMM. Subsequently, Lagrangian dispersion simulations for a set of air pollutants and emission sectors (traffic, industry, ...) based on extremely detailed building and emission data was performed in GRAL. The result of this nested procedure is a library of 3-dimensional air pollution maps representative of hourly situations in Zurich (Berchet et al. 2017). From these pre-computed situations, time-series and concentration maps can be obtained by selecting situations according to observed or modelled meteorological conditions.</p><p>The results were compared to measurements from air quality monitoring network stations. Modelled concentrations of NO<sub>x</sub> and PM compared well to measurements across multiple locations, provided background conditions were considered carefully. The nested multi-scale modelling system COSMO-ART/GRAMM/GRAL can adequately reproduce local air quality and help understanding the relative contributions of local versus distant emissions, as well as fill the space between precise point measurements from monitoring sites. This information is useful for research, policy-making, and epidemiological studies particularly under the assumption that exceedingly high concentrations become more and more localised phenomenon in the future.</p>


2019 ◽  
Vol 19 (2) ◽  
pp. 119-127 ◽  
Author(s):  
Surya K Ghosh ◽  
Daniel Jost

Abstract Understanding how genomes fold and organize is one of the main challenges in modern biology. Recent high-throughput techniques like Hi-C, in combination with cutting-edge polymer physics models, have provided access to precise information on 3D chromosome folding to decipher the mechanisms driving such multi-scale organization. In particular, structural maintenance of chromosome (SMC) proteins play an important role in the local structuration of chromatin, putatively via a loop extrusion process. Here, we review the different polymer physics models that investigate the role of SMCs in the formation of topologically associated domains (TADs) during interphase via the formation of dynamic loops. We describe the main physical ingredients, compare them and discuss their relevance against experimental observations.


2018 ◽  
Author(s):  
T. King ◽  
C.J. Leonard ◽  
J.C. Cooper ◽  
S. Nguyen ◽  
E. Joyce ◽  
...  

AbstractCondensins play a crucial role in the organization of genetic material by compacting and disentangling chromosomes. The condensin I and condensin II complexes are widely considered to have distinct functions based on studies in a few model organisms, although the specific functions of each complex are yet to be fully understood. The condensin II complex is critical for genome organization in Drosophila, and is a key anti-pairing factor that separates homologous chromosomes in somatic cells. Intriguingly, the Cap-G2 subunit of condensin II is absent in Drosophila melanogaster, and this loss may be related to the high levels of homologous chromosome pairing in somatic cells seen in flies. Here, we find that this Cap-G2 loss predates the origin of Dipterans, and other CapG2 losses have occurred independently in multiple insect lineages. Furthermore, the Cap-H2 and Cap-D3 subunits have also been repeatedly and independently lost in several insect orders, and some taxa lack condensin II-specific subunits entirely. We used Oligopaint DNA-FISH to quantify pairing levels in ten species across seven orders, representing several different configurations of the condensin II complex. We find that all non-Dipteran insects display near-uniform low pairing levels, suggesting that some key aspects of genome organization are robust to condensin II subunit losses. Finally, we observe consistent signatures of positive selection in condensin II subunits across flies and mammals. These findings suggest that these ancient complexes are far more evolutionarily labile than previously suspected, and are at the crossroads of several forms of genomic conflicts. Our results raise fundamental questions about the specific functions of the two condensin complexes and the interplay between them in taxa that have experienced subunit losses, and open the door to further investigations to elucidate the diversity of molecular mechanisms that underlie genome organization across various life forms.


2020 ◽  
Vol 48 (5) ◽  
pp. e26-e26
Author(s):  
Vipin Kumar ◽  
Simon Leclerc ◽  
Yuichi Taniguchi

Abstract High-throughput chromosome conformation capture (Hi-C) technology enables the investigation of genome-wide interactions among chromosome loci. Current algorithms focus on topologically associating domains (TADs), that are contiguous clusters along the genome coordinate, to describe the hierarchical structure of chromosomes. However, high resolution Hi-C displays a variety of interaction patterns beyond what current TAD detection methods can capture. Here, we present BHi-Cect, a novel top-down algorithm that finds clusters by considering every locus with no assumption of genomic contiguity using spectral clustering. Our results reveal that the hierarchical structure of chromosome is organized as ‘enclaves’, which are complex interwoven clusters at both local and global scales. We show that the nesting of local clusters within global clusters characterizing enclaves, is associated with the epigenomic activity found on the underlying DNA. Furthermore, we show that the hierarchical nesting that links different enclaves integrates their respective function. BHi-Cect provides means to uncover the general principles guiding chromatin architecture.


2005 ◽  
Vol 25 (21) ◽  
pp. 9283-9291 ◽  
Author(s):  
Elena Kravchenko ◽  
Ekaterina Savitskaya ◽  
Oksana Kravchuk ◽  
Alexander Parshikov ◽  
Pavel Georgiev ◽  
...  

ABSTRACT The Suppressor of the Hairy wing [Su(Hw)] binding region within the gypsy retrotransposon is the best known chromatin insulator in Drosophila melanogaster. According to previous data, two copies of the gypsy insulator inserted between an enhancer and a promoter neutralize each other's actions, which is indicative of an interaction between the protein complexes bound to the insulators. We have investigated the role of pairing between the gypsy insulators located on homologous chromosomes in trans interaction between yellow enhancers and a promoter. It has been shown that trans activation of the yellow promoter strongly depends on the site of the transposon insertion, which is evidence for a role of surrounding chromatin in homologous pairing. The presence of the gypsy insulators in both homologous chromosomes even at a distance of 9 kb downstream from the promoter dramatically improves the trans activation of yellow. Moreover, the gypsy insulators have proved to stabilize trans activation between distantly located enhancers and a promoter. These data suggest that gypsy insulator pairing is involved in communication between loci in the Drosophila genome.


2006 ◽  
Vol 04 (02) ◽  
pp. 317-333 ◽  
Author(s):  
ZHONG CHEN ◽  
YING XU

As the first step toward a multi-scale, hierarchical computational approach for membrane protein structure prediction, the packing of transmembrane helices was modeled at the residue and atom levels, respectively. For predictions at the residue level, the helix-helix and helix-membrane interactions were described by a set of knowledge-based energy functions. For predictions at the atom level, CHARMM19 force field was used. To facilitate the system to overcome energy barriers, the Wang–Landau method was employed, where a random walk is performed in the energy space with a uniform probability. Native-like structures were predicted at both levels for two model systems, each of which consists of two transmembrane helices. Interestingly, consistent results were obtained from simulations at the residue and atom levels for the same system, strongly suggesting the feasibility of a hierarchical approach for membrane protein structure predictions.


2009 ◽  
Vol 328 (2) ◽  
pp. 518-528 ◽  
Author(s):  
Sheryl T. Smith ◽  
Priyankara Wickramasinghe ◽  
Andrew Olson ◽  
Dmitri Loukinov ◽  
Lan Lin ◽  
...  

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 1025-1038 ◽  
Author(s):  
J A Kassis

Abstract We have previously shown that a 2-kb fragment of engrailed DNA can suppress expression of a linked marker gene, white, in the P element vector CaSpeR. This suppression is dependent on the presence of two copies of engrailed DNA-containing P elements (P[en]) in proximity in the Drosophila genome (either in cis or in trans). In this study, the 2-kb fragment was dissected and found to contain three fragments of DNA which could mediate white suppression [called "pairing-sensitive sites" (PS)]. A PS site was also identified in regulatory DNA from the Drosophila escargot gene. The eye colors of six different P[en] insertions in the escargot gene suggest an interaction between P[en]-encoded and genome-encoded PS sites. I hypothesize that white gene expression from P[en] is repressed by the formation of a protein complex which is initiated at the engrailed PS sites and also requires interactions with flanking genomic DNA. Genes were sought which influence the function of PS sites. Mutations in some Polycomb and trithorax group genes were found to affect the eye color from some P[en] insertion sites. However, different mutations affected expression from different P[en] insertion sites and no one mutation was found to affect expression from all P[en] insertion sites examined. These results suggest that white expression from P[en] is not directly regulated by members of the Polycomb and trithorax group genes, but in some cases can be influenced by them. I propose that engrailed PS sites normally act to promote interactions between distantly located engrailed regulatory sites and the engrailed promoter.


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