scholarly journals Principles of genome folding into topologically associating domains

2019 ◽  
Vol 5 (4) ◽  
pp. eaaw1668 ◽  
Author(s):  
Quentin Szabo ◽  
Frédéric Bantignies ◽  
Giacomo Cavalli
Keyword(s):  
Size Structure ◽  
Genome Structure ◽  
Cell Nuclei ◽  
Chromosome Conformation ◽  
Chromatin Interactions ◽  
Topologically Associating Domains ◽  
Wide Range ◽  
Genome Activity ◽  
And Function ◽  
Capture Techniques

Understanding the mechanisms that underlie chromosome folding within cell nuclei is essential to determine the relationship between genome structure and function. The recent application of “chromosome conformation capture” techniques has revealed that the genome of many species is organized into domains of preferential internal chromatin interactions called “topologically associating domains” (TADs). This chromosome chromosome folding has emerged as a key feature of higher-order genome organization and function through evolution. Although TADs have now been described in a wide range of organisms, they appear to have specific characteristics in terms of size, structure, and proteins involved in their formation. Here, we depict the main features of these domains across species and discuss the relation between chromatin structure, genome activity, and epigenome, highlighting mechanistic principles of TAD formation. We also consider the potential influence of TADs in genome evolution.

scholarly journals SisterC: A novel 3C-technique to detect chromatin interactions between and along sister chromatids

2020 ◽  
Author(s):  
Marlies E. Oomen ◽  
Adam K. Hedger ◽  
Jonathan K. Watts ◽  
Job Dekker
Keyword(s):  
Cell Cycle ◽  
Single Strand ◽  
Chromosome Conformation Capture ◽  
Brdu Incorporation ◽  
Chromosome Conformation ◽  
Strand Breaks ◽  
Chromatin Interactions ◽  
Sister Chromatids ◽  
Single Strand Breaks ◽  
Capture Techniques

Abstract Current chromosome conformation capture techniques are not able to distinguish sister chromatids. Here we describe the protocol of SisterC1: a novel Hi-C technique that leverages BrdU incorporation and UV/Hoechst-induced single strand breaks to identify interactions along and between sister chromatids. By synchronizing cells, BrdU is incorporated only on the newly replicated strand, which distinguishes the two sister chromatids2,3. This is followed by Hi-C4 of cells that can be arrested in different stages of the cell cycle, e.g. in mitosis. Before final amplification of the Hi-C library, strands containing BrdU are specifically depleted by UV/Hoechst treatment. SisterC libraries are then sequenced using 50bp paired end reads, followed by mapping using standard Hi-C processing tools. Interactions can then be assigned as inter- or intra-sister interactions based on read orientation.

scholarly journals Functional organization of the human 4D Nucleome

2015 ◽  
Vol 112 (26) ◽  
pp. 8002-8007 ◽  
Author(s):  
Haiming Chen ◽  
Jie Chen ◽  
Lindsey A. Muir ◽  
Scott Ronquist ◽  
Walter Meixner ◽  
...  
Keyword(s):  
3D Imaging ◽  
Functional Organization ◽  
Genome Structure ◽  
Structural Features ◽  
Topological Stability ◽  
Chromosome Conformation ◽  
Dynamical Interaction ◽  
Gene Pairs ◽  
Genome Wide ◽  
And Function

The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression.

scholarly journals The interdependent nature of multi-loci associations can be revealed by 4C-Seq

2015 ◽  
Author(s):  
Tingting Jiang ◽  
Ramya Raviram ◽  
Pedro P Rocha ◽  
Valentina Snetkova ◽  
Charlotte Proudhon ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Population Based ◽  
Data Sets ◽  
Low Resolution ◽  
Chromosome Conformation ◽  
Chromatin Interactions ◽  
Pairwise Interactions ◽  
Capture Techniques ◽  
Transcriptional Output ◽  
Resolution Single

Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that these associations act in isolation of other interacting partners within the genome. Indeed, the influence of multi-loci interactions in gene control remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise interactions involving the Tcrb and Igk antigen receptor enhancers, in addition to novel tri-loci associations. We further show that enhancer deletions not only interfere with tri-loci interactions in which they participate, but they also disrupt pairwise interactions between other partner enhancers and this disruption is linked to a reduction in their transcriptional output. These findings underscore the functional importance of hubs and provide new insight into chromatin organization as a whole. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings.

scholarly journals Mitochondrial DNA in the bark weevils: size, structure and heteroplasmy.

Genetics ◽  
1989 ◽  
Vol 123 (4) ◽  
pp. 825-836 ◽  
Author(s):  
T M Boyce ◽  
M E Zwick ◽  
C F Aquadro
Keyword(s):  
Mitochondrial Dna ◽  
Rare Variants ◽  
Size Structure ◽  
Genome Structure ◽  
Size Variation ◽  
Gene Content ◽  
Coding Region ◽  
Rich Region ◽  
Large Size ◽  
And Function

Abstract Mitochondrial DNA of higher animals has been described as an example of extreme efficiency in genome structure and function. Where exceptionally large size molecules have been found (greater than 20 kb), most have occurred as rare variants within a species, suggesting that these variants arise infrequently and do not persist for long periods in evolutionary time. In contrast, all individuals of at least three species of bark weevil (Curculionidae: Pissodes) possess a mitochondrial genome of unusually large size (30-36 kb). The molecule owes its large size to a dramatically enlarged A + T-rich region (9-13 kb). Gene content and order outside of this region appear to be identical to that found in Drosophila. A series of 0.8-2.0-kb repeated sequences occur adjacent to the large A + T rich region and have perhaps played a role in the generation of the large size as well as an unprecedented frequency of size variant heteroplasmy. Every weevil sampled in all three species (n = 219) exhibits anywhere from two to five distinct size classes of mtDNA. The persistence of this large amount of size polymorphism through two speciation events combined with the abundant size variation within individuals suggests that these molecules may not be subject to strong selection for small overall size and efficiency of replication. This pattern of variation contrasts strongly with the conservation of gene content and arrangement in the coding region of the molecule.

scholarly journals 4DNvestigator: Time Series Hi-C and RNA-seq Data Analysis Toolbox

2020 ◽  
Author(s):  
Stephen Lindsly ◽  
Scott Ronquist ◽  
Sijia Liu ◽  
Samuel Dilworth ◽  
Michael Perlman ◽  
...  
Keyword(s):  
Time Series ◽  
Data Analysis ◽  
Genomic Structure ◽  
Genome Structure ◽  
Single Layer ◽  
Cell Phenotype ◽  
Rna Seq ◽  
Chromosome Conformation ◽  
Network Entropy ◽  
And Function

AbstractMotivationComprehensive investigation of genome structure and function dynamics underlying cell phenotype produces vast amounts of high-dimensional, multilayered data. New methods are required to organize these data into an informative framework. Here we provide a comprehensive data analysis toolbox guided by theory of networks.ResultsWe present the “4DNvestigator”, a user-friendly toolbox for the analysis of time-series genome structure, measured by genome-wide chromosome conformation capture (Hi-C), and genome function, measured by RNA sequencing (RNA-seq). Our toolbox provides network-based data analysis tools such as single-layer/multilayer network centrality and network entropy to characterize the 4D Nucleome. The toolbox also contains statistical methods for comparing genomic structure at multiple genomic scales.Availabilityhttps://github.com/lindsly/[email protected]

scholarly journals Topologically associating domains and their role in the evolution of genome structure and function in Drosophila

2020 ◽  
Author(s):  
Yi Liao ◽  
Xinwen Zhang ◽  
Mahul Chakraborty ◽  
J.J. Emerson
Keyword(s):  
Genome Structure ◽  
Three Dimensional ◽  
Genomic Analysis ◽  
Purifying Selection ◽  
Drosophila Species ◽  
Comparative Genomic ◽  
Topologically Associating Domains ◽  
Transcript Structure ◽  
And Function ◽  
Long Genes

Topologically associating domains (TADs) were recently identified as fundamental units of three-dimensional eukaryotic genomic organization, though our knowledge of the influence of TADs on genome evolution remains preliminary. To study the molecular evolution of TADs in Drosophila species, we constructed a new reference-grade genome assembly and accompanying high-resolution TAD map for D. pseudoobscura. Comparison of D. pseudoobscura and D. melanogaster, which are separated by ~49 million years of divergence, showed that ~30-40% of their genomes retain conserved TADs. Comparative genomic analysis of 17 Drosophila species revealed that chromosomal rearrangement breakpoints are enriched at TAD boundaries but depleted within TADs. Additionally, genes within conserved TADs exhibit lower expression divergence than those located in nonconserved TADs. Furthermore, we found that a substantial proportion of long genes (>50 kbp) in D. melanogaster (42%) and D. pseudoobscura (26%) constitute their own TADs, implying transcript structure may be one of the deterministic factors for TAD formation. Using structural variants (SVs) identified from 14 D. melanogaster strains, its 3 closest sibling species from the D. simulans species complex, and two obscura clade species, we uncovered evidence of selection acting on SVs at TAD boundaries, but with the nature of selection differing between SV types. Deletions are depleted at TAD boundaries in both divergent and polymorphic SVs, suggesting purifying selection, whereas divergent tandem duplications are enriched at TAD boundaries relative to polymorphism, suggesting they are adaptive. Our findings highlight how important TADs are in shaping the acquisition and retention of structural mutations that fundamentally alter genome organization.

Chaperonin as the normal controls and pathological anti-stress response in the human reproductive system

2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  
Keyword(s):  
Reproductive System ◽  
Stress Proteins ◽  
Physiological Stress ◽  
Protein Complexes ◽  
Reproductive Function ◽  
Intercellular Signaling ◽  
Toll Like Receptors ◽  
Wide Range ◽  
Protein Functions ◽  
And Function

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.

Possession and Repetition

2012 ◽  
Vol 6 (1-3) ◽  
pp. 243-259 ◽  
Author(s):  
Yohan Yoo
Keyword(s):  
First Century ◽  
Daily Lives ◽  
Modern Times ◽  
Sacred Texts ◽  
New Methods ◽  
Wide Range ◽  
Lay Buddhists ◽  
Iconic Status ◽  
And Function ◽  
To Receive

This article demonstrates the need for the iconic status and function of Buddhist scripture to receive more attention by illuminating how lay Korean Buddhists try to appropriate the power of sutras. The oral and aural aspects of scripture, explained by Wilfred Cantwell Smith, provide only a limited understanding of the characteristics of scripture. It should be noted that, before modern times, most lay people, not only in Buddhist cultures but also in Christian and other traditions, neither had the chance to recite scriptures nor to listen to their recitations regularly. Several clear examples demonstrate contemporary Korean Buddhists’ acceptance of the iconic status of sutras and their attempt to appropriate the power and status of those sacred texts. In contemporary Korea, lay Buddhists try to claim the power of scriptures in their daily lives by repeating and possessing them. Twenty-first century lay believers who cannot read or recite in a traditional style have found new methods of repetition, such as internet programs for copying sacred texts and for playing recordings of their recitations. In addition, many Korean Buddhists consider the act of having sutras in one’s possession to be an effective way of accessing the sacred status and power of these texts. Hence, various ways of possessing them have been developed in a wide range of products, from fancy gilded sutras to sneakers embroidered with mantras.

The Art of Love Poetry

2018 ◽  
Author(s):  
Erik Gray
Keyword(s):  
Popular Culture ◽  
Cultural History ◽  
Literary Tradition ◽  
Love Poetry ◽  
Erotic Love ◽  
Wide Range ◽  
History Of ◽  
And Function ◽  
Meaning And Function ◽  
Comprehensive History

Love begets poetry; poetry begets love. These two propositions have seemed evident to thinkers and poets across the Western literary tradition. Plato writes that “anyone that love touches instantly becomes a poet.” And even today, when poetry has largely disappeared from the mainstream of popular culture, it retains its romantic associations. But why should this be so—what are the connections between poetry and erotic love that lead us to associate them so strongly with one another? An examination of different theories of both love and poetry across the centuries reveals that the connection between them is not merely an accident of cultural history—the result of our having grown up hearing, or hearing about, love poetry—but something more intrinsic. Even as definitions of them have changed, the two phenomena have consistently been described in parallel terms. Love is characterized by paradox. Above all, it is both necessarily public, because interpersonal, and intensely private; hence it both requires expression and resists it. In poetry, especially lyric poetry, which features its own characteristic paradoxes and silences, love finds a natural outlet. This study considers both the theories and the love poems themselves, bringing together a wide range of examples from different eras in order to examine the major structures that love and poetry share. It does not aim to be a comprehensive history of Western love poetry, but an investigation into the meaning and function of recurrent tropes, forms, and images employed by poets to express and describe erotic love.

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