Chromatin as an active polymeric material

2020 ◽  
Vol 4 (2) ◽  
pp. 111-118
Author(s):  
Gautam I. Menon
Keyword(s):  
Large Scale ◽  
Transcriptional Activity ◽  
Spatial Organization ◽  
Nuclear Architecture ◽  
Chromosome Territories ◽  
X Chromosomes ◽  
Equilibrium Processes ◽  
Territorial Organization ◽  
Differential Positioning ◽  
Radial Separation

The patterns of the large-scale spatial organization of chromatin in interphase human somatic cells are not random. Such patterns include the radial separation of euchromatin and heterochromatin, the territorial organization of individual chromosomes, the non-random locations of chromosome territories and the differential positioning of the two X chromosomes in female cells. These features of large-scale nuclear architecture follow naturally from the hypothesis that ATP-consuming non-equilibrium processes associated with highly transcribed regions of chromosomes are a source of ‘active’ forces. These forces are in excess of those that arise from Brownian motion. Simulations of model chromosomes that incorporate such activity recapitulate these features. In addition, they reproduce many other aspects of the spatial organization of chromatin at large scales that are known from experiments. Our results, reviewed here, suggest that the distribution of transcriptional activity across chromosomes underlies many aspects of large-scale nuclear architecture that were hitherto believed to be unrelated.

scholarly journals A First-principles Approach to Large-scale Nuclear Architecture

2018 ◽  
Author(s):  
Ankit Agrawal ◽  
Nirmalendu Ganai ◽  
Surajit Sengupta ◽  
Gautam I. Menon
Keyword(s):  
First Principles ◽  
Large Scale ◽  
Transcriptional Activity ◽  
Nuclear Architecture ◽  
Cell Type ◽  
Cell Nuclei ◽  
Differential Positioning ◽  
Cell Type Specific ◽  
Active Processes ◽  
Stochastic Forces

AbstractModel approaches to nuclear architecture have traditionally ignored the biophysical consequences of ATP-fueled active processes acting on chromatin. However, transcription-coupled activity is a source of stochastic forces that are substantially larger than the Brownian forces present at physiological temperatures. Here, we describe a first-principles approach to large-scale nuclear architecture in metazoans that incorporates cell-type-specific active processes. The model predicts the statistics of positional distributions, shapes and overlaps of each chromosome. Our simulations reproduce common organising principles underlying large-scale nuclear architecture across human cell nuclei in interphase. These include the differential positioning of euchromatin and heterochromatin, the territorial organisation of chromosomes including both gene-density-based and size-based chromosome radial positioning schemes, the non-random locations of chromosome territories and the shape statistics of individual chromosomes. We propose that the biophysical consequences of the distribution of transcriptional activity across chromosomes should be central to any chromosome positioning code.

scholarly journals Nuclear Organization of Mammalian Genomes

1999 ◽  
Vol 146 (6) ◽  
pp. 1211-1226 ◽  
Author(s):  
Nicolas Sadoni ◽  
Sabine Langer ◽  
Christine Fauth ◽  
Giorgio Bernardi ◽  
Thomas Cremer ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Chromosome Structure ◽  
Nuclear Architecture ◽  
Replication Timing ◽  
Cell Types ◽  
Higher Order ◽  
Chromosome Territories ◽  
Mitotic Chromosomes ◽  
Organizational Principle ◽  
Mammalian Genomes

We investigated the nuclear higher order compartmentalization of chromatin according to its replication timing (Ferreira et al. 1997) and the relations of this compartmentalization to chromosome structure and the spatial organization of transcription. Our aim was to provide a comprehensive and integrated view on the relations between chromosome structure and functional nuclear architecture. Using different mammalian cell types, we show that distinct higher order compartments whose DNA displays a specific replication timing are stably maintained during all interphase stages. The organizational principle is clonally inherited. We directly demonstrate the presence of polar chromosome territories that align to build up higher order compartments, as previously suggested (Ferreira et al. 1997). Polar chromosome territories display a specific orientation of early and late replicating subregions that correspond to R- or G/C-bands of mitotic chromosomes. Higher order compartments containing G/C-bands replicating during the second half of the S phase display no transcriptional activity detectable by BrUTP pulse labeling and show no evidence of transcriptional competence. Transcriptionally competent and active chromatin is confined to a coherent compartment within the nuclear interior that comprises early replicating R-band sequences. As a whole, the data provide an integrated view on chromosome structure, nuclear higher order compartmentalization, and their relation to the spatial organization of functional nuclear processes.

scholarly journals Spatial Organization of Large-Scale Chromatin Domains in the Nucleus: A Magnified View of Single Chromosome Territories

1997 ◽  
Vol 139 (7) ◽  
pp. 1597-1610 ◽  
Author(s):  
João Ferreira ◽  
Giovanni Paolella ◽  
Carlos Ramos ◽  
Angus I. Lamond
Keyword(s):  
Transcriptional Activation ◽  
Large Scale ◽  
Spatial Organization ◽  
Chinese Hamster ◽  
Spatial Separation ◽  
Peripheral Compartment ◽  
Chromosome Territories ◽  
Chromatin Domains ◽  
Single Chromosome ◽  
Band Size

We have analyzed the spatial organization of large scale chromatin domains in chinese hamster fibroblast, human lymphoid (IM-9), and marsupial kidney epithelial (PtK) cells by labeling DNA at defined stages of S phase via pulsed incorporation of halogenated deoxynucleosides. Most, if not all, chromosomes contribute multiple chromatin domains to both peripheral and internal nucleoplasmic compartments. The peripheral compartment contains predominantly late replicating G/Q bands, whereas early replicating R bands preferentially localize to the internal nucleoplasmic compartment. During mitosis, the labeled chromatin domains that were separated in interphase form a pattern of intercalated bands along the length of each metaphase chromosome. The transition from a banded (mitotic) to a compartmentalized (interphasic) organization of chromatin domains occurs during the late telophase/early G1 stage and is independent of transcriptional activation of the genome. Interestingly, generation of micronuclei with a few chromosomes showed that the spatial separation of early and late replicating chromatin compartments is recapitulated independently of chromosome number, even in micronuclei containing only a single chromosome. Our data strongly support the notion that the compartmentalization of large-scale (band size) chromatin domains seen in the intact nucleus is a magnified image of a similar compartmentalization occurring in individual chromosome territories.

scholarly journals Chromatin loop anchors contain core structural components of the gene expression machinery in maize

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stéphane Deschamps ◽  
John A. Crow ◽  
Nadia Chaidir ◽  
Brooke Peterson-Burch ◽  
Sunil Kumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Transcriptional Activity ◽  
Spatial Organization ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Maize Genome ◽  
Chromatin Loop ◽  
Structural Components ◽  
Chromatin Loops

Abstract Background Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity. Results Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that < 7% of all loops detected here are potentially devoid of any genes or regulatory elements. The overall organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions. Conclusions Sets of conserved chromatin loop anchors mapping to hierarchical domains contains core structural components of the gene expression machinery in maize. The data presented here will be a useful reference to further investigate their function in regard to the formation of transcriptional complexes and the regulation of transcriptional activity in the maize genome.

XBP-1 increases ERα transcriptional activity through regulation of large-scale chromatin unfolding

2004 ◽  
Vol 323 (1) ◽  
pp. 269-274 ◽  
Author(s):  
Yan Fang ◽  
Jinghua Yan ◽  
Lihua Ding ◽  
Yufei Liu ◽  
Jianhua Zhu ◽  
...  
Keyword(s):  
Large Scale ◽  
Transcriptional Activity

Spatial organization of rural territories

2021 ◽  
pp. 751-756
Author(s):  
Sevostyanov A.V. Sevostyanov A.V. ◽  
V.A. Sevostyanov ◽  
A.P. Spiridonova
Keyword(s):  
Scale Development ◽  
Rural Population ◽  
Large Scale ◽  
Spatial Organization ◽  
Low Density ◽  
Rural Settlements ◽  
Residential Areas ◽  
Complex Development

This article covers the issues raised by the objectives of the "The Program for complex development of rural territories" and its subprogram "Providing rural population with affordable and comfortable housing". The authors substantiate the concept "rural agglomeration" and make the suggestions on how to choose rural settlements and land plots suitable for large-scale development of low-density residential areas.

scholarly journals High-throughput super-resolution analysis of influenza virus pleomorphism reveals insights into viral spatial organization

2021 ◽  
Author(s):  
Andrew McMahon ◽  
Rebecca Andrews ◽  
Sohail V Ghani ◽  
Thorben Cordes ◽  
Achillefs N Kapanidis ◽  
...  
Keyword(s):  
Large Scale ◽  
Spatial Organization ◽  
Structural Information ◽  
Virus Assembly ◽  
Super Resolution ◽  
Automated Analysis ◽  
Size Analysis ◽  
Analysis Pipeline ◽  
Single Experiment ◽  
Viral Immunology

Many viruses form highly pleomorphic particles; in influenza, these particles range from spheres of ~ 100 nm in diameter to filaments of several microns in length. Virion structure is of interest, not only in the context of virus assembly, but also because pleomorphic variations may correlate with infectivity and pathogenicity. Detailed images of virus morphology often rely on electron microscopy, which is generally low throughput and limited in molecular identification. We have used fluorescence super-resolution microscopy combined with a rapid automated analysis pipeline to image many thousands of individual influenza virions, gaining information on their size, morphology and the distribution of membrane-embedded and internal proteins. This large-scale analysis revealed that influenza particles can be reliably characterised by length, that no spatial frequency patterning of the surface glycoproteins occurs, and that RNPs are preferentially located towards filament ends within Archetti bodies. Our analysis pipeline is versatile and can be adapted for use on multiple other pathogens, as demonstrated by its application for the size analysis of SARS-CoV-2. The ability to gain nanoscale structural information from many thousands of viruses in just a single experiment is valuable for the study of virus assembly mechanisms, host cell interactions and viral immunology, and should be able to contribute to the development of viral vaccines, anti-viral strategies and diagnostics.

scholarly journals Emerin modulates spatial organization of chromosome territories in cells on softer matrices

2018 ◽  
Vol 46 (11) ◽  
pp. 5561-5586 ◽  
Author(s):  
Roopali Pradhan ◽  
Devika Ranade ◽  
Kundan Sengupta
Keyword(s):  
Spatial Organization ◽  
Chromosome Territories ◽  
In Cells

Alteration of nuclear architecture in male germ cells of chromosomally derived subfertile mice

2001 ◽  
Vol 114 (24) ◽  
pp. 4429-4434
Author(s):  
Silvia Garagna ◽  
Maurizio Zuccotti ◽  
Alan Thornhill ◽  
Raul Fernandez-Donoso ◽  
Soledad Berrios ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Spatial Organization ◽  
Nuclear Architecture ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Condensed State ◽  
Germ Cell Differentiation ◽  
Y Chromosomes ◽  
Dual Colour ◽  
Pachytene Spermatocytes

The mammalian cell nucleus consists of numerous compartments involved in the regular unfolding of processes such as DNA replication and transcription, RNA maturation, protein synthesis and cell division. Knowledge is increasing of the relationships between high-order levels of chromatin organization and its spatial organization, and of how these relationships contribute to the various functions carried out in the nucleus. We have studied the spatial arrangement of mouse telocentric chromosomes 5, 11, 13, 15, 16 and 17, some of their metacentric Robertsonian derivatives, and X and Y chromosomes by whole chromosome painting in male germ (spermatogonia, pachytene spermatocytes and spermatids) and Sertoli cells of homozygous and heterozygous individuals. Using dual-colour fluorescence in situ hybridization we found that these chromosomes occupy specific nuclear territories in each cell type analysed. When chromosomes are present as Robertsonian metacentrics in the heterozygous state, that is, as Robertsonian metacentrics and their homologous telocentrics, differences in their nuclear positions are detectable: heterozygosity regularly produces a change in the nuclear position of one of the two homologous telocentrics in all the cell types studied. In the Robertsonian heterozygotes, the vast majority of the Sertoli cells show the sex chromosomes in a condensed state, whereas they appear decondensed in the Robertsonian homozygotes. As the Robertsonian heterozygosities we studied produce a chromosomally derived impairment of male germ-cell differentiation, we discuss the possibility that changes in chromosome spatial territories may alter some nuclear machinery (e.g., synapsis, differential gene expression) important for the correct unfolding of the meiotic process and for the proper functioning of Sertoli cells.

Functional domains of a T-DNA promoter active in crown gall tumors

1987 ◽  
Vol 7 (1) ◽  
pp. 59-67
Author(s):  
W B Bruce ◽  
W B Gurley
Keyword(s):  
Promoter Activity ◽  
Large Scale ◽  
Transcriptional Activity ◽  
Transcriptional Start Site ◽  
Internal Standard ◽  
Significant Loss ◽  
Internal Deletion ◽  
Substitution Mutations ◽  
Tata Motif ◽  
A Minor

Promoter domains required for transcriptional expression of the 780 gene of T-right (pTi15955) were identified by deletion mutagenesis. Accurate quantitation of transcriptional activity of a series of 5' and internal deletion mutants was achieved by using a double gene vector containing a reference 780 gene as an internal standard. Results of the 5' deletions delineated an activator element located between -440 and -229 base pairs (bp) from the start of transcription. Removal of this region resulted in a 100-fold decrease in promoter activity. Two relatively small internal deletion/substitution mutations at positions -74 to -76 and -98 to -112 reduced promoter activity to 38 and 42%, respectively. In most cases large-scale internal deletions (38 to 151 bp) occurring in various locations from positions -12 to -348 bp caused a significant loss in major promoter activity. However, three internal deletions starting at position -37 and extending upstream as far as -153 bp either had little effect on transcriptional activity or resulted in increased activity. Removal of the TATA motif drastically reduced promoter activity to less than 0.1% of the wild type. A minor start of transcription was detected 60 bases upstream from the major transcriptional start site. This minor promoter shares the same activator element as the major promoter for full activity. Deletion and insertion mutations downstream of the minor promoter TATA demonstrated the role of the TATA box in positioning the start of transcription.

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