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 ◽  
...  

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.

2021 ◽  
Vol 22 (21) ◽  
pp. 11585
Author(s):  
Tapan Kumar Mohanta ◽  
Awdhesh Kumar Mishra ◽  
Ahmed Al-Harrasi

The genome is the most functional part of a cell, and genomic contents are organized in a compact three-dimensional (3D) structure. The genome contains millions of nucleotide bases organized in its proper frame. Rapid development in genome sequencing and advanced microscopy techniques have enabled us to understand the 3D spatial organization of the genome. Chromosome capture methods using a ligation approach and the visualization tool of a 3D genome browser have facilitated detailed exploration of the genome. Topologically associated domains (TADs), lamin-associated domains, CCCTC-binding factor domains, cohesin, and chromatin structures are the prominent identified components that encode the 3D structure of the genome. Although TADs are the major contributors to 3D genome organization, they are absent in Arabidopsis. However, a few research groups have reported the presence of TAD-like structures in the plant kingdom.


2021 ◽  
Author(s):  
Alyssa D. Casill ◽  
Adam J. Haimowitz ◽  
Brian Kosmyna ◽  
Charles C. Query ◽  
Kenny Ye ◽  
...  

SummaryThe organization of the genome in three-dimensional space has been shown to play an important role in gene expression. Specifically, facets of genomic interaction such as topologically associated domains (TADs) have been shown to regulate transcription by bringing regulatory elements into close proximity1. mRNA production is an intricate process with multiple control points including regulation of Pol II elongation and the removal of non-coding sequences via pre-mRNA splicing2. The connection between genomic compartments and the kinetics of RNA biogenesis and processing has been largely unexplored. Here, we measure Pol II elongation and splicing kinetics genome-wide using a novel technique that couples nascent RNA-seq with a mathematical model of transcription and co-transcriptional RNA processing. We uncovered multiple layers of spatial organization of these rates: the rate of splicing is coordinated across introns within individual genes, and both elongation and splicing rates are coordinated within TADs, as are alternative splicing outcomes. Overall, our work establishes that the kinetics of transcription and splicing are coordinated by the spatial organization of the genome and suggests that TADs are a major platform for coordination of alternative splicing.


2019 ◽  
Author(s):  
Dong-Qing Sun ◽  
Liu Tian ◽  
Bin-Guang Ma

AbstractTranscriptional regulatory network (TRN) is a directed complex network composed of all regulatory interactions between transcription factors and corresponding target genes. Recently, the three-dimensional (3D) genomics studies have shown that the 3D structure of the genome makes a difference to the regulation of gene transcription, which provides us with a novel perspective. In this study, we constructed the TRN of the budding yeast Saccharomyces cerevisiae and placed it in the context of 3D genome model. We analyzed the spatial organization of the yeast TRN on four levels: global feature, central nodes, hierarchical structure and network motifs. Our results suggested that the TRN of S. cerevisiae presents an optimized structure in space to adapt to functional requirement.


2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jonas Paulsen ◽  
Monika Sekelja ◽  
Anja R. Oldenburg ◽  
Alice Barateau ◽  
Nolwenn Briand ◽  
...  

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.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Agnieszka A. Golicz ◽  
Prem L. Bhalla ◽  
David Edwards ◽  
Mohan B. Singh

AbstractGenomes of many eukaryotic species have a defined three-dimensional architecture critical for cellular processes. They are partitioned into topologically associated domains (TADs), defined as regions of high chromatin inter-connectivity. While TADs are not a prominent feature of A. thaliana genome organization, they have been reported for other plants including rice, maize, tomato and cotton and for which TAD formation appears to be linked to transcription and chromatin epigenetic status. Here we show that in the rice genome, sequence variation and meiotic recombination rate correlate with the 3D genome structure. TADs display increased SNP and SV density and higher recombination rate compared to inter-TAD regions. We associate the observed differences with the TAD epigenetic landscape, TE composition and an increased incidence of meiotic crossovers.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Emre Sefer

AbstractChromosome conformation capture experiments such as Hi–C map the three-dimensional spatial organization of genomes in a genome-wide scale. Even though Hi–C interactions are not biased towards any of the histone modifications, previous analysis has revealed denser interactions around many histone modifications. Nevertheless, simultaneous effects of these modifications in Hi–C interaction graph have not been fully characterized yet, limiting our understanding of genome shape. Here, we propose ChromatinCoverage and its extension TemporalPrizeCoverage methods to decompose Hi–C interaction graph in terms of known histone modifications. Both methods are based on set multicover with pairs, where each Hi–C interaction is tried to be covered by histone modification pairs. We find 4 histone modifications H3K4me1, H3K4me3, H3K9me3, H3K27ac to be significantly predictive of most Hi–C interactions across species, cell types and cell cycles. The proposed methods are quite effective in predicting Hi–C interactions and topologically-associated domains in one species, given it is trained on another species or cell types. Overall, our findings reveal the impact of subset of histone modifications in chromatin shape via Hi–C interaction graph.


2019 ◽  
Author(s):  
J. Yuyang Lu ◽  
Lei Chang ◽  
Tong Li ◽  
Ting Wang ◽  
Yafei Yin ◽  
...  

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.


2019 ◽  
Vol 35 (23) ◽  
pp. 4912-4921 ◽  
Author(s):  
M Nuriddinov ◽  
V Fishman

Abstract Motivation Recent development of Hi-C technique, a biochemical method to study 3D genome architecture, provided large amount of information describing spatial organization of chromosomes in different cell types and species. While multiple tools are available for analysis and comparison of Hi-C data of different cell types, there are almost no resources for systematic interspecies comparison. Results To fill this gap, we developed C-InterSecture, a computational pipeline allowing systematic comparison of genome architecture between species. C-InterSecture allows statistical comparison of contact frequencies of individual pairs of loci, as well as interspecies comparison of contacts pattern within defined genomic regions, i.e. topologically associated domains. We employed C-InterSecture to compare mammalian and avian genome organization and showed how evolutionary changes of genomic distance affect 3D architecture of vertebrate’s genome. Availability and implementation C-InterSecture is implemented as a collection of python scripts freely available on GitHub repository at https://github.com/NuriddinovMA/C-InterSecture. Jucebox-compatible .hic files produced by C-InterSecture are available at http://genedev.bionet.nsc.ru/site/CIntersecture.html. Supplementary information Supplementary data are available at Bioinformatics online.


2020 ◽  
Vol 11 ◽  
Author(s):  
América Ramírez-Colmenero ◽  
Katarzyna Oktaba ◽  
Selene L. Fernandez-Valverde

Long non-coding RNAs (lncRNAs) have important regulatory functions across eukarya. It is now clear that many of these functions are related to gene expression regulation through their capacity to recruit epigenetic modifiers and establish chromatin interactions. Several lncRNAs have been recently shown to participate in modulating chromatin within the spatial organization of the genome in the three-dimensional space of the nucleus. The identification of lncRNA candidates is challenging, as it is their functional characterization. Conservation signatures of lncRNAs are different from those of protein-coding genes, making identifying lncRNAs under selection a difficult task, and the homology between lncRNAs may not be readily apparent. Here, we review the evidence for these higher-order genome organization functions of lncRNAs in animals and the evolutionary signatures they display.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sambhavi Animesh ◽  
Ruchi Choudhary ◽  
Bertrand Jern Han Wong ◽  
Charlotte Tze Jia Koh ◽  
Xin Yi Ng ◽  
...  

Nasopharyngeal cancer (NPC), a cancer derived from epithelial cells in the nasopharynx, is a cancer common in China, Southeast Asia, and Africa. The three-dimensional (3D) genome organization of nasopharyngeal cancer is poorly understood. A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method for the characterization of chromatin interactions in solid cancer needle biopsy samples. Here, we developed Biop-C, a modified in situ Hi-C method using solid cancer needle biopsy samples. We applied Biop-C to characterize three nasopharyngeal cancer solid cancer needle biopsy patient samples. We identified topologically associated domains (TADs), chromatin interaction loops, and frequently interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from the Biop-C heatmaps. We observed that the genomic features are shared at some important oncogenes, but the patients also display extensive heterogeneity at certain genomic loci. On analyzing the super enhancer landscape in nasopharyngeal cancer cell lines, we found that the super enhancers are associated with FIREs and can be linked to distal genes via chromatin loops in NPC. Taken together, our results demonstrate the utility of our Biop-C method in investigating 3D genome organization in solid cancers.


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