scholarly journals Plant 3-D Chromatin Organization: Important Insights from Chromosome Conformation Capture Analyses of the Last 10 Years

2021 ◽  
Author(s):  
Xinxin Zhang ◽  
Tianzuo Wang
Keyword(s):  
Genome Organization ◽  
Gene Expression Regulation ◽  
Epigenetic Modification ◽  
Three Dimensional ◽  
Chromatin Organization ◽  
Chromatin Conformation ◽  
D Genome ◽  
Chromatin Domains ◽  
Chromosome Conformation ◽  
Chromatin Conformation Capture

Abstract Over the past few decades, eukaryotic linear genomes and epigenomes have been widely and extensively studied for understanding gene expression regulation. More recently, the three-dimensional (3-D) chromatin organization was found to be important for determining genome functionality, finely tuning physiological processes for appropriate cellular responses. With the development of visualization techniques and chromatin conformation capture (3C)-based techniques, increasing evidence indicates that chromosomal architecture characteristics and chromatin domains with different epigenetic modification in the nucleus are correlated to transcriptional activities. Subsequent studies have further explored the intricate interplay between 3-D genome organization and the function of interacting regions. In this review, we summarize spatial distribution patterns of chromatin, including chromatin positioning, configurations and domains, with a particular focus on the effect of a unique form of interaction between a variety of factors that shapes the 3-D genome conformation in plants. We further discuss the methods, advantages and limitations of various chromatin conformation capture (3C)-based techniques, highlighting the applications of these technologies in plants to identify chromatin domains, and address their dynamic changes and functional implications in evolution, and adaptation to development and changing environmental conditions. Moreover, the future implications and emerging research directions of 3-D genome organization are discussed.

scholarly journals Technologies to study spatial genome organization: beyond 3C

2019 ◽  
Author(s):  
Nadine Übelmesser ◽  
Argyris Papantonis
Keyword(s):  
Genome Organization ◽  
Nuclear Organization ◽  
Three Dimensional ◽  
Nuclear Space ◽  
Chromosome Conformation ◽  
Novel Variants ◽  
Cell Processes ◽  
Systematic Biases ◽  
And Function ◽  
Spatial Genome Organization

Abstract The way that chromatin is organized in three-dimensional nuclear space is now acknowledged as a factor critical for the major cell processes, like transcription, replication and cell division. Researchers have been armed with new molecular and imaging technologies to study this structure-to-function link of genomes, spearheaded by the introduction of the ‘chromosome conformation capture’ technology more than a decade ago. However, this technology is not without shortcomings, and novel variants and orthogonal approaches are being developed to overcome these. As a result, the field of nuclear organization is constantly fueled by methods of increasing resolution and/or throughput that strive to eliminate systematic biases and increase precision. In this review, we attempt to highlight the most recent advances in technology that promise to provide novel insights on how chromosomes fold and function.

scholarly journals The three-dimensional genome organization of Drosophila melanogaster through data integration

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Qingjiao Li ◽  
Harianto Tjong ◽  
Xiao Li ◽  
Ke Gong ◽  
Xianghong Jasmine Zhou ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Data Integration ◽  
Genome Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Structural Features ◽  
Embryonic Cells ◽  
Data Types ◽  
Chromosome Conformation ◽  
Topological Domains

Abstract Background Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome’s organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Results Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Conclusions Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

scholarly journals Associating disease-related genetic variants in intergenic regions to the genes they impact

2014 ◽  
Author(s):  
Geoff Macintyre ◽  
Antonio Jimeno Yepes ◽  
Cheng Soon Ong ◽  
Karin Verspoor
Keyword(s):  
Genetic Variants ◽  
Target Genes ◽  
Three Dimensional ◽  
Biomedical Literature ◽  
Dimensional Structure ◽  
Chromatin Conformation ◽  
Functional Interpretation ◽  
Chromatin Conformation Capture ◽  
Intergenic Regions ◽  
Small Test

We present a method to assist in interpretation of the functional impact of intergenic disease-associated SNPs that is not limited to search strategies proximal to the SNP. The method builds on two sources of external knowledge: the growing understanding of three-dimensional spatial relationships in the genome, and the substantial repository of information about relationships among genetic variants, genes, and diseases captured in the published biomedical literature. We integrate chromatin conformation capture data (HiC) with literature support to rank putative target genes of intergenic disease-associated SNPs. We demonstrate that this hybrid method outperforms a genomic distance baseline on a small test set of expression quantitative trait loci, as well as either method individually. In addition, we show the potential for this method to uncover relationships between intergenic SNPs and target genes across chromosomes. With more extensive chromatin conformation capture data becoming readily available, this method provides a way forward towards functional interpretation of SNPs in the context of the three dimensional structure of the genome in the nucleus.

scholarly journals Simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization

2020 ◽  
Author(s):  
Da-Inn Lee ◽  
Sushmita Roy
Keyword(s):  
High Throughput ◽  
Matrix Factorization ◽  
Genome Organization ◽  
Time Course ◽  
Critical Role ◽  
Chromatin Modification ◽  
Three Dimensional ◽  
Enrichment Analysis ◽  
Developmental Time ◽  
Chromosome Conformation

AbstractThe three-dimensional (3D) organization of the genome plays a critical role in gene regulation for diverse normal and disease processes. High-throughput chromosome conformation capture (3C) assays, such as Hi-C, SPRITE, GAM, and HiChIP, have revealed higher-order organizational units such as topologically associating domains (TADs), which can shape the regulatory landscape governing downstream phenotypes. Analysis of high-throughput 3C data depends on the sequencing depth, which directly affects the resolution and the sparsity of the generated 3D contact count map. Identification of TADs remains a significant challenge due to the sensitivity of existing methods to resolution and sparsity. Here we present GRiNCH, a novel matrix-factorization-based approach for simultaneous TAD discovery and smoothing of contact count matrices from high-throughput 3C data. GRiNCH TADs are enriched in known architectural proteins and chromatin modification signals and are stable to the resolution, and sparsity of the input data. GRiNCH smoothing improves the recovery of structure and significant interactions from low-depth datasets. Furthermore, enrichment analysis of 746 transcription factor motifs in GRiNCH TADs from developmental time-course and cell-line Hi-C datasets predicted transcription factors with potentially novel genome organization roles. GRiNCH is a broadly applicable tool for the analysis of high throughput 3C datasets from a variety of platforms including SPRITE and HiChIP to understand 3D genome organization in diverse biological contexts.

scholarly journals Lamins organize the global three-dimensional genome from the nuclear periphery

2017 ◽  
Author(s):  
Xiaobin Zheng ◽  
Jiabiao Hu ◽  
Sibiao Yue ◽  
Lidya Kristiani ◽  
Miri Kim ◽  
...  
Keyword(s):  
Genome Organization ◽  
Es Cells ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Nuclear Lamina ◽  
Chromatin Domain ◽  
List Type ◽  
Chromatin Domains ◽  
Mouse Es Cells ◽  
Domain Interactions

AbstractLamins are structural components of the nuclear lamina (NL) that regulate genome organization and gene expression, but the mechanism remains unclear. Using Hi-C, we show that lamins maintain proper interactions among the topologically associated chromatin domains (TADs) but not their overall architecture. Combining Hi-C with fluorescence in situ hybridization (FISH) and analyses of lamina-associated domains (LADs), we reveal that lamin loss causes expansion or detachment of specific LADs in mouse ES cells. The detached LADs disrupt 3D interactions of both LADs and interior chromatin. 4C and epigenome analyses further demonstrate that lamins maintain the active and repressive chromatin domains among different TADs. By combining these studies with transcriptome analyses, we found a significant correlation between transcription changes and the changes of active and inactive chromatin domain interactions. These findings provide a foundation to further study how the nuclear periphery impacts genome organization and transcription in development and NL-associated diseases.HighlightsLamin loss does not affect the overall TAD structure but alters TAD-TAD interactionsLamin null ES cells exhibit decondensation or detachment of specific LAD regionsExpansion and detachment of LADs can alter genome-wide 3D chromatin interactionsAltered chromatin domain interactions are correlated with altered transcription

scholarly journals DNA methylation in transposable elements disrupts the connection between three-dimensional chromatin organization and gene expression upon rice genome duplication.

2021 ◽  
Author(s):  
Zhenfei Sun ◽  
Yunlong Wang ◽  
Zhaojian Song ◽  
Hui Zhang ◽  
Min Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Genome Duplication ◽  
Rice Genome ◽  
Three Dimensional ◽  
Plant Evolution ◽  
Chromatin Organization ◽  
Regulatory Sequences ◽  
Chromosome Conformation ◽  
Significant Difference

Polyploidy serves as a major force in plant evolution and domestication of cultivated crops. However, the relationship and underlying mechanism between three-dimensional (3D) chromatin organization and gene expression upon rice genome duplication is largely unknown. Here we compared the 3D chromatin structures between diploid (2C) and autotetraploid (4C) rice by high-throughput chromosome conformation capture analysis, and found that 4C rice presents weakened intra-chromosomal interactions compared to its 2C progenitor. Moreover, we found that changes of 3D chromatin organizations including chromatin compartments, topologically associating domain (TAD) and loops uncouple from gene expression. Moreover, DNA methylations in the regulatory sequences of genes in compartment A/B switched regions and TAD boundaries are not related to their expressions. Importantly, in contrast to that there was no significant difference of methylation levels in TEs in promoters of differentially expressed genes (DEGs) and non-DEGs between 2C and 4C rice, we found that the hypermethylated transposable elements across genes in compartment A/B switched regions and TAD boundaries suppress the expression of these genes. We propose that the rice genome doubling might modulate TE methylation which results in the disconnection between the alteration of 3D chromatin structure and gene expression.

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 MethHaplo: combining allele-specific DNA methylation and SNPs for haplotype region identification

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiangwei Zhou ◽  
Ze Wang ◽  
Jing Li ◽  
Wing-Kin Sung ◽  
Guoliang Li
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Three Dimensional ◽  
Hybrid Vigor ◽  
Nucleotide Polymorphisms ◽  
Chromosome Conformation ◽  
Genome Bisulfite Sequencing ◽  
Allele Specific ◽  
Eukaryotic Organisms

Abstract Background DNA methylation is an important epigenetic modification that plays a critical role in most eukaryotic organisms. Parental alleles in haploid genomes may exhibit different methylation patterns, which can lead to different phenotypes and even different therapeutic and drug responses to diseases. However, to our knowledge, no software is available for the identification of DNA methylation haplotype regions with combined allele-specific DNA methylation, single nucleotide polymorphisms (SNPs) and high-throughput chromosome conformation capture (Hi-C) data. Results In this paper, we developed a new method, MethHaplo, that identify DNA methylation haplotype regions with allele-specific DNA methylation and SNPs from whole-genome bisulfite sequencing (WGBS) data. Our results showed that methylation haplotype regions were ten times longer than haplotypes with SNPs only. When we integrate WGBS and Hi-C data, MethHaplo could call even longer haplotypes. Conclusions This study illustrates the usefulness of methylation haplotypes. By constructing methylation haplotypes for various cell lines, we provide a clearer picture of the effect of DNA methylation on gene expression, histone modification and three-dimensional chromosome structure at the haplotype level. Our method could benefit the study of parental inheritance-related disease and hybrid vigor in agriculture.

scholarly journals Associating disease-related genetic variants in intergenic regions to the genes they impact

2014 ◽  
Author(s):  
Geoff Macintyre ◽  
Antonio Jimeno Yepes ◽  
Cheng Soon Ong ◽  
Karin Verspoor
Keyword(s):  
Genetic Variants ◽  
Target Genes ◽  
Three Dimensional ◽  
Biomedical Literature ◽  
Dimensional Structure ◽  
Chromatin Conformation ◽  
Functional Interpretation ◽  
Chromatin Conformation Capture ◽  
Intergenic Regions ◽  
Small Test

We present a method to assist in interpretation of the functional impact of intergenic disease-associated SNPs that is not limited to search strategies proximal to the SNP. The method builds on two sources of external knowledge: the growing understanding of three-dimensional spatial relationships in the genome, and the substantial repository of information about relationships among genetic variants, genes, and diseases captured in the published biomedical literature. We integrate chromatin conformation capture data (HiC) with literature support to rank putative target genes of intergenic disease-associated SNPs. We demonstrate that this hybrid method outperforms a genomic distance baseline on a small test set of expression quantitative trait loci, as well as either method individually. In addition, we show the potential for this method to uncover relationships between intergenic SNPs and target genes across chromosomes. With more extensive chromatin conformation capture data becoming readily available, this method provides a way forward towards functional interpretation of SNPs in the context of the three dimensional structure of the genome in the nucleus.

Sign in / Sign up

Export Citation Format

Share Document