scholarly journals Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jonas Paulsen ◽  
Monika Sekelja ◽  
Anja R. Oldenburg ◽  
Alice Barateau ◽  
Nolwenn Briand ◽  
...  
Keyword(s):  
Single Cells ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Modeling Framework ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Spatial Features ◽  
Nuclear Lamin ◽  
Topologically Associated Domains ◽  
User Friendly

Abstract Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.

scholarly journals Sci-Hi-C: a single-cell Hi-C method for mapping 3D genome organization in large number of single cells

2019 ◽  
Author(s):  
Vijay Ramani ◽  
Xinxian Deng ◽  
Ruolan Qiu ◽  
Choli Lee ◽  
Christine M Disteche ◽  
...  
Keyword(s):  
Single Cell ◽  
Genome Organization ◽  
Single Cells ◽  
Three Dimensional ◽  
Population Based ◽  
Order Structure ◽  
Chromosome Conformation ◽  
3D Genome ◽  
A Cell ◽  
Cell To Cell Variability

AbstractThe highly dynamic nature of chromosome conformation and three-dimensional (3D) genome organization leads to cell-to-cell variability in chromatin interactions within a cell population, even if the cells of the population appear to be functionally homogeneous. Hence, although Hi-C is a powerful tool for mapping 3D genome organization, this heterogeneity of chromosome higher order structure among individual cells limits the interpretive power of population based bulk Hi-C assays. Moreover, single-cell studies have the potential to enable the identification and characterization of rare cell populations or cell subtypes in a heterogeneous population. However, it may require surveying relatively large numbers of single cells to achieve statistically meaningful observations in single-cell studies. By applying combinatorial cellular indexing to chromosome conformation capture, we developed single-cell combinatorial indexed Hi-C (sci-Hi-C), a high throughput method that enables mapping chromatin interactomes in large number of single cells. We demonstrated the use of sci-Hi-C data to separate cells by karytoypic and cell-cycle state differences and to identify cellular variability in mammalian chromosomal conformation. Here, we provide a detailed description of method design and step-by-step working protocols for sci-Hi-C.

scholarly journals Reorganization of chromosome architecture in replicative cellular senescence

2016 ◽  
Vol 2 (2) ◽  
pp. e1500882 ◽  
Author(s):  
Steven W. Criscione ◽  
Marco De Cecco ◽  
Benjamin Siranosian ◽  
Yue Zhang ◽  
Jill A. Kreiling ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Structural Model ◽  
Three Dimensional ◽  
Chromatin Accessibility ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
Topologically Associated Domains ◽  
Chromosomal Architecture ◽  
Fundamental Biological Process ◽  
3D Architecture

Replicative cellular senescence is a fundamental biological process characterized by an irreversible arrest of proliferation. Senescent cells accumulate a variety of epigenetic changes, but the three-dimensional (3D) organization of their chromatin is not known. We applied a combination of whole-genome chromosome conformation capture (Hi-C), fluorescence in situ hybridization, and in silico modeling methods to characterize the 3D architecture of interphase chromosomes in proliferating, quiescent, and senescent cells. Although the overall organization of the chromatin into active (A) and repressive (B) compartments and topologically associated domains (TADs) is conserved between the three conditions, a subset of TADs switches between compartments. On a global level, the Hi-C interaction matrices of senescent cells are characterized by a relative loss of long-range and gain of short-range interactions within chromosomes. Direct measurements of distances between genetic loci, chromosome volumes, and chromatin accessibility suggest that the Hi-C interaction changes are caused by a significant reduction of the volumes occupied by individual chromosome arms. In contrast, centromeres oppose this overall compaction trend and increase in volume. The structural model arising from our study provides a unique high-resolution view of the complex chromosomal architecture in senescent cells.

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals Impact of Chromosome Fusions on 3D Genome Organization and Gene Expression in Budding Yeast

Genetics ◽  
2020 ◽  
Vol 214 (3) ◽  
pp. 651-667 ◽  
Author(s):  
Marco Di Stefano ◽  
Francesca Di Giovanni ◽  
Vasilisa Pozharskaia ◽  
Mercè Gomar-Alba ◽  
Davide Baù ◽  
...  
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Nuclear Organization ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Global Gene Expression ◽  
3D Genome ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Chromosome Fusions

The three-dimensional (3D) organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remain debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization and global gene expression in budding yeast containing chromosome fusions. We used computational modeling and single-cell imaging to determine chromosome positions, and integrated these data with genome-wide transcriptional profiles from RNA sequencing. We find that chromosome fusions dramatically alter 3D nuclear organization without leading to strong genome-wide changes in transcription. However, we observe a mild but significant and reproducible increase in the expression of genes displaced away from the periphery. The increase in transcription is inversely proportional to the propensity of a given locus to be at the nuclear periphery; for example, a 10% decrease in the propensity of a gene to reside at the nuclear envelope is accompanied by a 10% increase in gene expression. Modeling suggests that this is due to both deletion of telomeres and to displacement of genes relative to the nuclear periphery. These data suggest that basal transcriptional activity is sensitive to radial changes in gene position, and provide insight into the functional relevance of budding yeast chromosome-level 3D organization in gene expression.

scholarly journals The dynamic three-dimensional organization of the diploid yeast genome

2016 ◽  
Author(s):  
Seungsoo Kim ◽  
Ivan Liachko ◽  
Donna G Brickner ◽  
Kate Cook ◽  
William S Noble ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Yeast Genome ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Chromosome Conformation ◽  
Homolog Pairing ◽  
Pore Complexes ◽  
Eukaryotic Genomes

AbstractThe budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. Even in this well-studied model, it is unclear how homolog pairing in diploids and environment-induced gene relocalization influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation, we observe significant homolog proximity that increased in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1 alleles specifically under galactose induction and saturated growth, mediated by association with nuclear pore complexes at the nuclear periphery. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization.

scholarly journals Chromatin spatial organization of wild type and mutant peanuts reveals high-resolution genomic architecture and interaction alterations

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xingguo Zhang ◽  
Manish K. Pandey ◽  
Jianping Wang ◽  
Kunkun Zhao ◽  
Xingli Ma ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Gene Expression Regulation ◽  
Three Dimensional ◽  
Active Regions ◽  
Mutant Line ◽  
Binding Motif ◽  
Wild Type ◽  
3D Genome ◽  
Topologically Associated Domains ◽  
High Gene

Abstract Background Three-dimensional (3D) chromatin organization provides a critical foundation to investigate gene expression regulation and cellular homeostasis. Results Here, we present the first 3D genome architecture maps in wild type and mutant allotetraploid peanut lines, which illustrate A/B compartments, topologically associated domains (TADs), and widespread chromatin interactions. Most peanut chromosomal arms (52.3%) have active regions (A compartments) with relatively high gene density and high transcriptional levels. About 2.0% of chromosomal regions switch from inactive to active (B-to-A) in the mutant line, harboring 58 differentially expressed genes enriched in flavonoid biosynthesis and circadian rhythm functions. The mutant peanut line shows a higher number of genome-wide cis-interactions than its wild-type. The present study reveals a new TAD in the mutant line that generates different chromatin loops and harbors a specific upstream AP2EREBP-binding motif which might upregulate the expression of the GA2ox gene and decrease active gibberellin (GA) content, presumably making the mutant plant dwarf. Conclusions Our findings will shed new light on the relationship between 3D chromatin architecture and transcriptional regulation in plants.

Three-dimensional chromosome organization in flowering plants

2020 ◽  
Vol 19 (2) ◽  
pp. 83-91 ◽  
Author(s):  
Stefan Grob
Keyword(s):  
Plant Species ◽  
De Novo ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Chromosome Organization ◽  
Data Sets ◽  
Comprehensive Overview ◽  
De Novo Genome Assembly ◽  
3D Genome ◽  
Wide Range

Abstract Research on plant three-dimensional (3D) genome architecture made rapid progress over the past 5 years. Numerous Hi-C interaction data sets were generated in a wide range of plant species, allowing for a comprehensive overview on 3D chromosome folding principles in the plant kingdom. Plants lack important genes reported to be vital for chromosome folding in animals. However, similar 3D structures such as topologically associating domains and chromatin loops were identified. Recent studies in Arabidopsis thaliana revealed how chromosomal regions are positioned within the nucleus by determining their association with both, the nuclear periphery and the nucleolus. Additionally, many plant species exhibit high-frequency interactions among KNOT entangled elements, which are associated with safeguarding the genome from invasive DNA elements. Many of the recently published Hi-C data sets were generated to aid de novo genome assembly and remain to date little explored. These data sets represent a valuable resource for future comparative studies, which may lead to a more profound understanding of the evolution of 3D chromosome organization in plants.

scholarly journals Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Can-hui Cao ◽  
Ye Wei ◽  
Rang Liu ◽  
Xin-ran Lin ◽  
Jia-qi Luo ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Ovary Syndrome ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Caucasian Women ◽  
Genome Interactions

Backgroundrs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined.MethodsThree-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns.ResultsGenerally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P<0.0001) and ovary (P=0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes (P=0.0002) and PCOS patients (P=0.0002), with CD4 high expression in PCOS patients (P=0.0316) and PCOS-like models (P=0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models (P=0.0178). Furthermore, androgen receptor (AR) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 (P=0.039) and FSHR (P=4e-06) in ovary tissues and PCOS-like mice.ConclusionOverall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

scholarly journals The repressive genome compartment is established early in the cell cycle before forming the lamina associated domains

2018 ◽  
Author(s):  
TR Luperchio ◽  
MEG Sauria ◽  
VE Hoskins ◽  
X Wong ◽  
E DeBoy ◽  
...  
Keyword(s):  
Live Cell Imaging ◽  
Cell Imaging ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Nuclear Lamina ◽  
Early Event ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Dynamic Relationship ◽  
Organizational Principles

AbstractThree-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.

scholarly journals GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data

2019 ◽  
Author(s):  
Oluwatosin Oluwadare ◽  
Max Highsmith ◽  
Jianlin Cheng
Keyword(s):  
Structure Prediction ◽  
Biological Activities ◽  
Genome Structure ◽  
3D Structure ◽  
Three Dimensional ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Reconstruction Methods ◽  
A Genome ◽  
Structure Reconstruction

ABSTRACTAdvances in the study of chromosome conformation capture (3C) technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional (3D) chromosome and genome structure reconstruction methods from Hi-C data. The 3D genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed. However, until now, there has been no freely available repository for 3D chromosome structures. In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. GSDB contains over 50,000 structures constructed by 12 state-of-the-art chromosome and genome structure prediction methods for publicly used Hi-C datasets with varying resolution. The database is useful for the community to study the function of genome from a 3D perspective. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB

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