Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains

Abstract Background CTCF binding contributes to the establishment of a higher-order genome structure by demarcating the boundaries of large-scale topologically associating domains (TADs). However, despite the importance and conservation of TADs, the role of CTCF binding in their evolution and stability remains elusive. Results We carry out an experimental and computational study that exploits the natural genetic variation across five closely related species to assess how CTCF binding patterns stably fixed by evolution in each species contribute to the establishment and evolutionary dynamics of TAD boundaries. We perform CTCF ChIP-seq in multiple mouse species to create genome-wide binding profiles and associate them with TAD boundaries. Our analyses reveal that CTCF binding is maintained at TAD boundaries by a balance of selective constraints and dynamic evolutionary processes. Regardless of their conservation across species, CTCF binding sites at TAD boundaries are subject to stronger sequence and functional constraints compared to other CTCF sites. TAD boundaries frequently harbor dynamically evolving clusters containing both evolutionarily old and young CTCF sites as a result of the repeated acquisition of new species-specific sites close to conserved ones. The overwhelming majority of clustered CTCF sites colocalize with cohesin and are significantly closer to gene transcription start sites than nonclustered CTCF sites, suggesting that CTCF clusters particularly contribute to cohesin stabilization and transcriptional regulation. Conclusions Dynamic conservation of CTCF site clusters is an apparently important feature of CTCF binding evolution that is critical to the functional stability of a higher-order chromatin structure.

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Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains

10.1101/668855 ◽

2019 ◽

Cited By ~ 3

Author(s):

Elissavet Kentepozidou ◽

Sarah J Aitken ◽

Christine Feig ◽

Klara Stefflova ◽

Ximena Ibarra-Soria ◽

...

Keyword(s):

Large Scale ◽

Evolutionary Dynamics ◽

Computational Study ◽

Genome Structure ◽

Higher Order ◽

Ctcf Binding ◽

Natural Genetic Variation ◽

Transcription Start Sites ◽

Topologically Associating Domains ◽

Species Specific

ABSTRACTCTCF binding contributes to the establishment of higher order genome structure by demarcating the boundaries of large-scale topologically associating domains (TADs). We have carried out an experimental and computational study that exploits the natural genetic variation across five closely related species to assess how CTCF binding patterns stably fixed by evolution in each species contribute to the establishment and evolutionary dynamics of TAD boundaries. We performed CTCF ChIP-seq in multiple mouse species to create genome-wide binding profiles and associated them with TAD boundaries. Our analyses reveal that CTCF binding is maintained at TAD boundaries by an equilibrium of selective constraints and dynamic evolutionary processes. Regardless of their conservation across species, CTCF binding sites at TAD boundaries are subject to stronger sequence and functional constraints compared to other CTCF sites. TAD boundaries frequently harbor rapidly evolving clusters containing both evolutionary old and young CTCF sites as a result of repeated acquisition of new species-specific sites close to conserved ones. The overwhelming majority of clustered CTCF sites colocalize with cohesin and are significantly closer to gene transcription start sites than nonclustered CTCF sites, suggesting that CTCF clusters particularly contribute to cohesin stabilization and transcriptional regulation. Overall, CTCF site clusters are an apparently important feature of CTCF binding evolution that are critical the functional stability of higher order chromatin structure.

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Functional signatures of evolutionarily young CTCF binding sites

10.1101/2020.01.31.928119 ◽

2020 ◽

Author(s):

Dhoyazan Azazi ◽

Jonathan M. Mudge ◽

Duncan T. Odom ◽

Paul Flicek

Keyword(s):

Mus Musculus ◽

Binding Sites ◽

Ctcf Binding ◽

Ctcf Binding Site ◽

Mus Musculus Domesticus ◽

Transcription Start Sites ◽

Regulatory Architecture ◽

Topologically Associated Domains ◽

Species Specific ◽

The Impact

ABSTRACTThe introduction of novel CTCF binding sites in gene regulatory regions in the rodent lineage is partly the effect of transposable element expansion. The exact mechanism and functional impact of evolutionarily novel CTCF binding sites are not yet fully understood. We investigated the impact of novel species-specific CTCF binding sites in two Mus genus subspecies, Mus musculus domesticus and Mus musculus castaneus, that diverged 0.5 million years ago. The activity of the B2-B4 family of transposable elements independently in both lineages leads to the proliferation of novel CTCF binding sites. A subset of evolutionarily young sites may harbour transcriptional functionality, as evidenced by the stability of their binding across multiple tissues in M. musculus domesticus (BL6), while overall the distance of species-specific CTCF binding to the nearest transcription start sites and/or topologically-associated domains (TADs) is largely similar to musculus-common CTCF sites. Remarkably, we discovered a recurrent regulatory architecture consisting of a CTCF binding site and an interferon gene that appears to have been tandemly duplicated to create a 15-gene cluster on chromosome 4, thus forming a novel BL6 specific immune locus, in which CTCF may play a regulatory role. Our results demonstrate that thousands of CTCF binding sites show multiple functional signatures rapidly after incorporation into the genome.

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The story of promiscuous crucifers: origin and genome evolution of an invasive species, Cardamine occulta (Brassicaceae), and its relatives

Annals of Botany ◽

10.1093/aob/mcz019 ◽

2019 ◽

Vol 124 (2) ◽

pp. 209-220 ◽

Cited By ~ 6

Author(s):

Terezie Mandáková ◽

Judita Zozomová-Lihová ◽

Hiroshi Kudoh ◽

Yunpeng Zhao ◽

Martin A Lysak ◽

...

Keyword(s):

Invasive Species ◽

Genome Evolution ◽

Large Scale ◽

Genome Structure ◽

Diploid Species ◽

Wide Distribution ◽

Ecological Niches ◽

Polyploid Evolution ◽

Weedy Species ◽

Species Specific

Abstract Background and Aims Cardamine occulta (Brassicaceae) is an octoploid weedy species (2n = 8x = 64) originated in Eastern Asia. It has been introduced to other continents including Europe and considered to be an invasive species. Despite its wide distribution, the polyploid origin of C. occulta remained unexplored. The feasibility of comparative chromosome painting (CCP) in crucifers allowed us to elucidate the origin and genome evolution in Cardamine species. We aimed to investigate the genome structure of C. occulta in comparison with its tetraploid (2n = 4x = 32, C. kokaiensis and C. scutata) and octoploid (2n = 8x = 64, C. dentipetala) relatives. Methods Genomic in situ hybridization (GISH) and large-scale CCP were applied to uncover the parental genomes and chromosome composition of the investigated Cardamine species. Key Results All investigated species descended from a common ancestral Cardamine genome (n = 8), structurally resembling the Ancestral Crucifer Karyotype (n = 8), but differentiated by a translocation between chromosomes AK6 and AK8. Allotetraploid C. scutata originated by hybridization between two diploid species, C. parviflora and C. amara (2n = 2x = 16). By contrast, C. kokaiensis has an autotetraploid origin from a parental genome related to C. parviflora. Interestingly, octoploid C. occulta probably originated through hybridization between the tetraploids C. scutata and C. kokaiensis. The octoploid genome of C. dentipetala probably originated from C. scutata via autopolyploidization. Except for five species-specific centromere repositionings and one pericentric inversion post-dating the polyploidization events, the parental subgenomes remained stable in the tetra- and octoploids. Conclusions Comparative genome structure, origin and evolutionary history was reconstructed in C. occulta and related species. For the first time, whole-genome cytogenomic maps were established for octoploid plants. Post-polyploid evolution in Asian Cardamine polyploids has not been associated with descending dysploidy and intergenomic rearrangements. The combination of different parental (sub)genomes adapted to distinct habitats provides an evolutionary advantage to newly formed polyploids by occupying new ecological niches.

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Characterizing higher order structures of chromatin in human cells

10.1101/267856 ◽

2018 ◽

Author(s):

Uwe Schwartz ◽

Attila Németh ◽

Sarah Diermeier ◽

Josef Exler ◽

Stefan Hansch ◽

...

Keyword(s):

Large Scale ◽

Structural Changes ◽

Computer Modelling ◽

Regulatory Elements ◽

Higher Order ◽

Chromatin Organization ◽

Transcription Start Sites ◽

Irregular Structure ◽

Genomic Regions ◽

Order Structures

AbstractPackaging of DNA into chromatin regulates DNA accessibility and, consequently, all DNA-dependent processes, such as transcription, recombination, repair, and replication. The nucleosome is the basic packaging unit of DNA forming arrays that are suggested, by biochemical studies, to fold hierarchically into ordered higher-order structures of chromatin. This defined organization of chromatin has been recently questioned using microscopy techniques, proposing a rather irregular structure. To gain more insight into the principles of chromatin organization, we applied an in situ differential MNase-seq strategy and analyzed in silico the results of complete and partial digestions of human chromatin. We investigated whether different levels of chromatin packaging exist in the cell. Thus, we assessed the accessibility of chromatin within distinct domains of kb to Mb genomic regions by utilizing statistical data analyses and computer modelling. We found no difference in the degree of compaction between domains of euchromatin and heterochromatin or between other sequence and epigenomic features of chromatin. Thus, our data suggests the absence of differentially compacted domains of higher-order structures of chromatin. Moreover, we identified only local structural changes, with individual hyper-accessible nucleosomes surrounding regulatory elements, such as enhancers and transcription start sites. The regulatory sites per se are occupied with structurally altered nucleosomes, exhibiting increased MNase sensitivity. Our findings provide biochemical evidence that supports an irregular model of large-scale chromatin organization.

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Accelerated Discovery of High-Refractive-Index Polyimides via First-Principles Molecular Modeling, Virtual High-Throughput Screening, and Data Mining

10.26434/chemrxiv.7670903.v1 ◽

2019 ◽

Author(s):

Mohammad Atif Faiz Afzal ◽

Mojtaba Haghighatlari ◽

Sai Prasad Ganesh ◽

Chong Cheng ◽

Johannes Hachmann

Keyword(s):

Data Mining ◽

Refractive Index ◽

High Throughput ◽

First Principles ◽

High Throughput Screening ◽

Large Scale ◽

Computational Study ◽

High Refractive Index ◽

Structural Features ◽

Learning Program

<div>We present a high-throughput computational study to identify novel polyimides (PIs) with exceptional refractive index (RI) values for use as optic or optoelectronic materials. Our study utilizes an RI prediction protocol based on a combination of first-principles and data modeling developed in previous work, which we employ on a large-scale PI candidate library generated with the ChemLG code. We deploy the virtual screening software ChemHTPS to automate the assessment of this extensive pool of PI structures in order to determine the performance potential of each candidate. This rapid and efficient approach yields a number of highly promising leads compounds. Using the data mining and machine learning program package ChemML, we analyze the top candidates with respect to prevalent structural features and feature combinations that distinguish them from less promising ones. In particular, we explore the utility of various strategies that introduce highly polarizable moieties into the PI backbone to increase its RI yield. The derived insights provide a foundation for rational and targeted design that goes beyond traditional trial-and-error searches.</div>

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Higher order Hamiltonian Monte Carlo sampling for cosmological large-scale structure analysis

Monthly Notices of the Royal Astronomical Society ◽

10.1093/mnras/stab123 ◽

2021 ◽

Vol 502 (3) ◽

pp. 3976-3992

Author(s):

Mónica Hernández-Sánchez ◽

Francisco-Shu Kitaura ◽

Metin Ata ◽

Claudio Dalla Vecchia

Keyword(s):

Fourth Order ◽

Large Scale ◽

Equations Of Motion ◽

Large Scale Structure ◽

Real Space ◽

Higher Order ◽

Second Order ◽

Scale Structure ◽

Integration Schemes ◽

Reconstruction Methods

ABSTRACT We investigate higher order symplectic integration strategies within Bayesian cosmic density field reconstruction methods. In particular, we study the fourth-order discretization of Hamiltonian equations of motion (EoM). This is achieved by recursively applying the basic second-order leap-frog scheme (considering the single evaluation of the EoM) in a combination of even numbers of forward time integration steps with a single intermediate backward step. This largely reduces the number of evaluations and random gradient computations, as required in the usual second-order case for high-dimensional cases. We restrict this study to the lognormal-Poisson model, applied to a full volume halo catalogue in real space on a cubical mesh of 1250 h−1 Mpc side and 2563 cells. Hence, we neglect selection effects, redshift space distortions, and displacements. We note that those observational and cosmic evolution effects can be accounted for in subsequent Gibbs-sampling steps within the COSMIC BIRTH algorithm. We find that going from the usual second to fourth order in the leap-frog scheme shortens the burn-in phase by a factor of at least ∼30. This implies that 75–90 independent samples are obtained while the fastest second-order method converges. After convergence, the correlation lengths indicate an improvement factor of about 3.0 fewer gradient computations for meshes of 2563 cells. In the considered cosmological scenario, the traditional leap-frog scheme turns out to outperform higher order integration schemes only when considering lower dimensional problems, e.g. meshes with 643 cells. This gain in computational efficiency can help to go towards a full Bayesian analysis of the cosmological large-scale structure for upcoming galaxy surveys.

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Evolutionary dynamics of higher-order interactions in social networks

Nature Human Behaviour ◽

10.1038/s41562-020-01024-1 ◽

2021 ◽

Author(s):

Unai Alvarez-Rodriguez ◽

Federico Battiston ◽

Guilherme Ferraz de Arruda ◽

Yamir Moreno ◽

Matjaž Perc ◽

...

Keyword(s):

Social Networks ◽

Evolutionary Dynamics ◽

Higher Order

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The Tomato Interspecific NB-LRR Gene Arsenal and Its Impact on Breeding Strategies

Genes ◽

10.3390/genes12020184 ◽

2021 ◽

Vol 12 (2) ◽

pp. 184

Author(s):

Giuseppe Andolfo ◽

Nunzio D’Agostino ◽

Luigi Frusciante ◽

Maria Raffaella Ercolano

Keyword(s):

Evolutionary Dynamics ◽

Special Focus ◽

Breeding Strategies ◽

Adaptive Diversification ◽

Solanum Lycopersicum L ◽

Solanaceae Species ◽

Specific Pathogen ◽

Adaptive Processes ◽

Species Specific ◽

R Loci

Tomato (Solanum lycopersicum L.) is a model system for studying the molecular basis of resistance in plants. The investigation of evolutionary dynamics of tomato resistance (R)-loci provides unique opportunities for identifying factors that promote or constrain genome evolution. Nucleotide-binding domain and leucine-rich repeat (NB-LRR) receptors belong to one of the most plastic and diversified families. The vast amount of genomic data available for Solanaceae and wild tomato relatives provides unprecedented insights into the patterns and mechanisms of evolution of NB-LRR genes. Comparative analysis remarked a reshuffling of R-islands on chromosomes and a high degree of adaptive diversification in key R-loci induced by species-specific pathogen pressure. Unveiling NB-LRR natural variation in tomato and in other Solanaceae species offers the opportunity to effectively exploit genetic diversity in genomic-driven breeding programs with the aim of identifying and introducing new resistances in tomato cultivars. Within this motivating context, we reviewed the repertoire of NB-LRR genes available for tomato improvement with a special focus on signatures of adaptive processes. This issue is still relevant and not thoroughly investigated. We believe that the discovery of mechanisms involved in the generation of a gene with new resistance functions will bring great benefits to future breeding strategies.

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Effects of Carrier Material and Design on Microalgae Attachment for Biofuel Manufacturing: A Literature Review

ASME 2010 International Manufacturing Science and Engineering Conference, Volume 1 ◽

10.1115/msec2010-34150 ◽

2010 ◽

Cited By ~ 2

Author(s):

Yan Cui ◽

Wenqiao Wayne Yuan ◽

Zhijian Pei

Keyword(s):

Free Energy ◽

Large Scale ◽

Cell Attachment ◽

Cost Effective ◽

Surface Wettability ◽

Biofuel Production ◽

Algae Biofuels ◽

Attachment Strength ◽

Species Specific ◽

Continuous Use

Continuous use of petroleum derived fuels is widely recognized as unsustainable due to depleting supplies and the accumulation of greenhouse gases in the environment. Renewable, carbon neutral transport fuels are needed for environmental and economic sustainabilities. Algae have been demonstrated to be one of the most promising sources for biofuel production. However, large-scale algae production and harvesting for energy manufacturing are too costly using existing methods. The approach of growing algae on solid carriers is innovative and can potentially lead to cost-effective manufacturing of algae biofuels. As cells approach to the solid surface, many factors come in to influence microbial attachment such as the surface wettability, free energy, polarity, roughness and topography. Surface wettability plays an important role in the initial cell attachment. For further contact, surface free energy and polarity are more directly related to cell-substratum attachment strength. Surface roughness and texture are species-specific parameters and have been applied widely in attachment studies.

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