Chromosome interactome inferred from mitosis-G1 transition

2016 ◽  
Author(s):  
Y.A. Eidelman ◽  
S.V. Slanina ◽  
A.V. Aleshchenko ◽  
S.G. Andreev
Keyword(s):  
Spatial Organization ◽  
Contact Map ◽  
Interphase Chromosome ◽  
Basic Principles ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Contact Patterns ◽  
Genome Wide ◽  
Genome Study ◽  
Contact Data

ABSTRACTThe progress in experimental techniques aimed at 3D genome study is yet to bring about revelation of basic principles of genome folding. Chromosome conformation capture Hi-C technologies provide genome wide mapping of genomic loci interactions but spatial organization of chromosomes remains unknown. Here, we develop a polymer modeling approach to generate the ensemble of 3D chromosome conformations for mapping genetic loci contacts and the positions of megabase chromosomal domains in interphase chromosome at different time of mitosis-interphase transition. We demonstrate that (*) whole chromosome contact map (interactome) generated for mouse chromosome 18 structure and (**) contact patterns, observed soon after mitotic decondensation and remaining similar during G1, correlate well with the experimental Hi-C contact data. The results suggest that contact map formation and spatial compartmentalization of an interphase chromosome are driven by interactions between different types of domains during formation of globular chromosome state at the end of mitotis-G1 transition.

scholarly journals Structural features of the fly chromatin colors revealed by automatic three-dimensional modeling.

2016 ◽  
Author(s):  
François Serra ◽  
Davide Baù ◽  
Guillaume Filion ◽  
Marc A. Marti-Renom
Keyword(s):  
Spatial Organization ◽  
Three Dimensional ◽  
Structural Features ◽  
Three Dimensions ◽  
Chromosome Conformation ◽  
Three Dimensional Modeling ◽  
Genomic Technologies ◽  
A Genome ◽  
Contact Data ◽  
Three Dimensional Models

The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three- dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, now permit to investigate the spatial organization of genomes. However, inferring structures from raw contact data is a tedious process for shortage of available tools. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions. To illustrate the use of TADbit, we automatically modeled 50 genomic domains from the fly genome revealing differential structural features of the previously defined chromatin colors, establishing a link between the conformation of the genome and the local chromatin composition. More generally, TADbit allows to obtain three-dimensional models ready for visualization from 3C-based experiments and to characterize their relation to gene expression and epigenetic states. TADbit is open-source and available for download from http://www.3DGenomes.org.

scholarly journals Topology, structures, and energy landscapes of human chromosomes

2015 ◽  
Vol 112 (19) ◽  
pp. 6062-6067 ◽  
Author(s):  
Bin Zhang ◽  
Peter G. Wolynes
Keyword(s):  
Liquid Crystalline ◽  
Spatial Organization ◽  
Human Chromosomes ◽  
Energy Landscapes ◽  
Interphase Chromosome ◽  
Chromosome Conformation ◽  
Information Theoretic ◽  
Knot Invariants ◽  
Topologically Associating Domains ◽  
And Topology

Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conformations based on the resulting information theoretic landscape not only accurately reproduce experimental contact probabilities, but also provide a picture of chromosome dynamics and topology. The topology of the simulated chromosomes is probed by computing the distribution of their knot invariants. The simulated chromosome structures are largely free of knots. Topologically associating domains are shown to be crucial for establishing these knotless structures. The simulated chromosome conformations exhibit a tendency to form fibril-like structures like those observed via light microscopy. The topologically associating domains of the interphase chromosome exhibit multistability with varying liquid crystalline ordering that may allow discrete unfolding events and the landscape is locally funneled toward “ideal” chromosome structures that represent hierarchical fibrils of fibrils.

scholarly journals SPIN reveals genome-wide landscape of nuclear compartmentalization

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuchuan Wang ◽  
Yang Zhang ◽  
Ruochi Zhang ◽  
Tom van Schaik ◽  
Liguo Zhang ◽  
...  
Keyword(s):  
Spatial Organization ◽  
K562 Cells ◽  
Replication Timing ◽  
Computational Method ◽  
Chromatin Interaction ◽  
Nuclear Speckles ◽  
Genome Spatial Organization ◽  
3D Genome ◽  
Genome Wide ◽  
Nuclear Compartmentalization

AbstractWe report SPIN, an integrative computational method to reveal genome-wide intranuclear chromosome positioning and nuclear compartmentalization relative to multiple nuclear structures, which are pivotal for modulating genome function. As a proof-of-principle, we use SPIN to integrate nuclear compartment mapping (TSA-seq and DamID) and chromatin interaction data (Hi-C) from K562 cells to identify 10 spatial compartmentalization states genome-wide relative to nuclear speckles, lamina, and putative associations with nucleoli. These SPIN states show novel patterns of genome spatial organization and their relation to other 3D genome features and genome function (transcription and replication timing). SPIN provides critical insights into nuclear spatial and functional compartmentalization.

scholarly journals Systematic evaluation of chromosome conformation capture assays

2020 ◽  
Author(s):  
Betul Akgol Oksuz ◽  
Liyan Yang ◽  
Sameer Abraham ◽  
Sergey V. Venev ◽  
Nils Krietenstein ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Cell Types ◽  
Chromosome Conformation Capture ◽  
Chromatin Interaction ◽  
Systematic Evaluation ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Experimental Parameters ◽  
Genome Features ◽  
Multiple Cell

AbstractChromosome conformation capture (3C)-based assays are used to map chromatin interactions genome-wide. Quantitative analyses of chromatin interaction maps can lead to insights into the spatial organization of chromosomes and the mechanisms by which they fold. A number of protocols such as in situ Hi-C and Micro-C are now widely used and these differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of experimental parameters of 3C-based protocols. We find that different protocols capture different 3D genome features with different efficiencies. First, the use of cross-linkers such as DSG in addition to formaldehyde improves signal-to-noise allowing detection of thousands of additional loops and strengthens the compartment signal. Second, fragmenting chromatin to the level of nucleosomes using MNase allows detection of more loops. On the other hand, protocols that generate larger multi-kb fragments produce stronger compartmentalization signals. We confirmed our results for multiple cell types and cell cycle stages. We find that cell type-specific quantitative differences in chromosome folding are not detected or underestimated by some protocols. Based on these insights we developed Hi-C 3.0, a single protocol that can be used to both efficiently detect chromatin loops and to quantify compartmentalization. Finally, this study produced ultra-deeply sequenced reference interaction maps using conventional Hi-C, Micro-C and Hi-C 3.0 for commonly used cell lines in the 4D Nucleome Project.

scholarly journals L1 and B1 repeats blueprint the spatial organization of chromatin

2019 ◽  
Author(s):  
J. Yuyang Lu ◽  
Lei Chang ◽  
Tong Li ◽  
Ting Wang ◽  
Yafei Yin ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Mammalian Cells ◽  
Spatial Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Order Structure ◽  
Basic Principles ◽  
Heterochromatin Protein ◽  
3D Genome ◽  
Genomic Repeats

SUMMARYDespite extensive mapping of three-dimensional (3D) chromatin structures, the basic principles underlying genome folding remain unknown. Here, we report a fundamental role for L1 and B1 retrotransposons in shaping the macroscopic 3D genome structure. Homotypic clustering of B1 and L1 repeats in the nuclear interior or at the nuclear and nucleolar peripheries, respectively, segregates the genome into mutually exclusive nuclear compartments. This spatial segregation of L1 and B1 is conserved in mouse and human cells, and occurs dynamically during establishment of the 3D chromatin structure in early embryogenesis and the cell cycle. Depletion of L1 transcripts drastically disrupts the spatial distributions of L1- and B1-rich compartments. L1 transcripts are strongly associated with L1 DNA sequences and induce phase separation of the heterochromatin protein HP1α. Our results suggest that genomic repeats act as the blueprint of chromatin macrostructure, thus explaining the conserved higher-order structure of chromatin across mammalian cells.

scholarly journals High resolution single-cell chromatin 3D modeling reveals coherent chromatin aggregation with varied structures in controlling genome function stability

2019 ◽  
Author(s):  
Luming Meng ◽  
Yi Shi ◽  
Chenxi Wang
Keyword(s):  
Single Cell ◽  
Gene Activation ◽  
Strongly Correlated ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Consistent Aggregation ◽  
3D Architecture ◽  
Genomic Regions

The genome 3D architecture is thought to be related to regulating gene expression levels in cells and can be explained by genome-wide chromatin interactions which have been explored by chromosome conformation capture based techniques, especially Hi-C. Based on single-cell Hi-C data, we developed a new method in constructing experimental consistent 3D intact genome structures for individual cells with a resolution of 10kb or higher. The modeled structures showed marked variations of 3D genome organization across different cells. However, chromosome loci marked by different proteins, such as CTCF and post-translationally modified histones, are consistently non-specifically aggregated in space. Interestingly, similar aggregations between active enhancers and active promoters were observed, especially for those separated by genomic regions of the scale of megabase or larger. Such long-range associations between active enhancers and promoters are strongly correlated with spatial aggregation of chromosome loci marked by different proteins. Through analyzing the 3D structures of intact genome, we proposed that coherent gene activation profiles among individual cells can be achieved by the consistent aggregation of protein marked loci instead of maintaining identical folded conformations.

scholarly journals Deciphering Multi-way Interactions in the Human Genome

2021 ◽  
Author(s):  
Stephen M Lindsly ◽  
Can Chen ◽  
Sam Dilworth ◽  
Sivakumar Jeyarajan ◽  
Cooper Stansbury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Genome ◽  
Human Fibroblasts ◽  
Data Representation ◽  
Chromatin Accessibility ◽  
Higher Order ◽  
Chromosome Conformation ◽  
Genome Wide ◽  
Binding Data ◽  
Contact Data

Chromatin architecture, a key regulator of gene expression, is inferred through chromatin contacts. However, classical analyses of chromosome conformation data do not preserve multi-way relationships. Here we use long sequencing reads to map genome-wide multi-way contacts and investigate higher order chromatin organization of the human genome. We use the theory of hypergraphs for data representation and analysis, and quantify higher order structures in primary human fibroblasts and B lymphocytes. Through integration of multi-way contact data with chromatin accessibility, gene expression, and transcription factor binding data, we introduce a data-driven method to extract transcriptional clusters.

scholarly journals HP1 drives de novo 3D genome reorganization in early Drosophila embryos

Nature ◽  
2021 ◽  
Author(s):  
Fides Zenk ◽  
Yinxiu Zhan ◽  
Pavel Kos ◽  
Eva Löser ◽  
Nazerke Atinbayeva ◽  
...  
Keyword(s):  
Genome Organization ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Early Embryo ◽  
Heterochromatin Protein ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Genome Reorganization

AbstractFundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. The binding of HP1a at pericentromeric heterochromatin is required to establish clustering of pericentromeric regions. Moreover, HP1a binding within chromosome arms is responsible for overall chromosome folding and has an important role in the formation of B-compartment regions. However, depletion of HP1a does not affect the A-compartment, which suggests that a different molecular mechanism segregates active chromosome regions. Our work identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early embryo.

scholarly journals Erythrocytes 3D genome organization in vertebrates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anastasia Ryzhkova ◽  
Alena Taskina ◽  
Anna Khabarova ◽  
Veniamin Fishman ◽  
Nariman Battulin
Keyword(s):  
Blood Cells ◽  
Genome Organization ◽  
Large Scale ◽  
Chromatin Condensation ◽  
Erythroid Differentiation ◽  
Interaction Patterns ◽  
3D Interaction ◽  
Interphase Chromosome ◽  
3D Genome ◽  
Contact Maps

AbstractGeneration of mature red blood cells, consisting mainly of hemoglobin, is a remarkable example of coordinated action of various signaling networks. Chromatin condensation is an essential step for terminal erythroid differentiation and subsequent nuclear expulsion in mammals. Here, we profiled 3D genome organization in the blood cells from ten species belonging to different vertebrate classes. Our analysis of contact maps revealed a striking absence of such 3D interaction patterns as loops or TADs in blood cells of all analyzed representatives. We also detect large-scale chromatin rearrangements in blood cells from mammals, birds, reptiles and amphibians: their contact maps display strong second diagonal pattern, representing an increased frequency of long-range contacts, unrelated to TADs or compartments. This pattern is completely atypical for interphase chromosome structure. We confirm that these principles of genome organization are conservative in vertebrate erythroid cells.

scholarly journals Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tejaswi Iyyanki ◽  
Baozhen Zhang ◽  
Qixuan Wang ◽  
Ye Hou ◽  
Qiushi Jin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Cancer Cell ◽  
Genome Structure ◽  
Transcription Factor Binding ◽  
Specific Gene ◽  
Open Chromatin ◽  
Factor Binding ◽  
3D Genome ◽  
Genome Wide

Abstract Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. Transcriptionally, FOXA1, GATA3, and PPARG are shown to be essential for luminal subtype-specific gene regulation and subtype switching, while TP63, STAT3, and TFAP2 family members are critical for regulation of basal subtype-specific genes. Despite these advances, the underlying epigenetic mechanisms and 3D chromatin architecture responsible for subtype-specific regulation in bladder cancer remain unknown. Result We determine the genome-wide transcriptome, enhancer landscape, and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration. Conclusion In summary, our work identifies unique epigenomic signatures and 3D genome structures in luminal and basal urinary bladder cancers and suggests a novel link between the circadian transcription factor NPAS2 and a clinical bladder cancer subtype.

Sign in / Sign up

Export Citation Format

Share Document