scholarly journals The 3D architecture of the pepper (Capsicum annum) genome and its relationship to function and evolution

2021 ◽  
Author(s):  
Yi Liao ◽  
Juntao Wang ◽  
Zhangsheng Zhu ◽  
Yuanlong Liu ◽  
Jinfeng Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dimensional Space ◽  
3D Structure ◽  
Three Dimensional ◽  
Structural Evolution ◽  
Integrated Analysis ◽  
Gene Clustering ◽  
Plant Genomes ◽  
3D Genome ◽  
Contact Maps

AbstractThe architecture of topologically associating domains (TADs) varies across plant genomes. Understanding the functional consequences of this diversity requires insights into the pattern, structure, and function of TADs. Here, we present a comprehensive investigation of the 3D genome organization of pepper (Capsicum annuum) and its association with gene expression and genomic variants. We report the first chromosome-scale long-read genome assembly of pepper and generate Hi-C contact maps for four tissues. The contact maps indicate that 3D structure varies somewhat across tissues, but generally the genome was segregated into subcompartments that were correlated with transcriptional state. In addition, chromosomes were almost continuously spanned by TADs, with the most prominent found in large genomic regions that were rich in retrotransposons. A substantial fraction of TAD boundaries were demarcated by chromatin loops, suggesting loop extrusion is a major mechanism for TAD formation; many of these loops were bordered by genes, especially in highly repetitive regions, resulting in gene clustering in three dimensional space. Integrated analysis of Hi-C profiles and transcriptomes showed that change in 3D chromatin structures (e.g. subcompartments, TADs, and loops) was not the primary mechanism contributing to differential gene expression between tissues, but chromatin structure does play a role in transcription stability. TAD boundaries were significantly enriched for breaks of synteny and depletion of sequence variation, suggesting that TADs constrain patterns of genome structural evolution in plants. Together, our work provides insights into principles of 3D genome folding in large plant genomes and its association with function and evolution.

scholarly journals Adenine DNA methylation, 3D genome organization, and gene expression in the parasiteTrichomonas vaginalis

2020 ◽  
Vol 117 (23) ◽  
pp. 13033-13043
Author(s):  
Ayelen Lizarraga ◽  
Zach Klapholz O’Brown ◽  
Konstantinos Boulias ◽  
Lara Roach ◽  
Eric Lieberman Greer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Trichomonas Vaginalis ◽  
Three Dimensional ◽  
Wide Distribution ◽  
Spatial Proximity ◽  
Regulation Of Transcription ◽  
3D Genome ◽  
Intergenic Regions ◽  
Close Spatial Proximity

Trichomonas vaginalisis a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5‐methylcytosine (5mC), is the main DNA methylation mark inT. vaginalis. Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA inT. vaginalisis associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.

scholarly journals Cell-Selective Regulation of CFTR Gene Expression: Relevance to Gene Editing Therapeutics

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 235 ◽  
Author(s):  
Hannah Swahn ◽  
Ann Harris
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Gene Editing ◽  
Genetic Diseases ◽  
3D Structure ◽  
Three Dimensional ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cftr Gene ◽  
Specific Expression

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is an attractive target for gene editing approaches, which may yield novel therapeutic approaches for genetic diseases such as cystic fibrosis (CF). However, for gene editing to be effective, aspects of the three-dimensional (3D) structure and cis-regulatory elements governing the dynamic expression of CFTR need to be considered. In this review, we focus on the higher order chromatin organization required for normal CFTR locus function, together with the complex mechanisms controlling expression of the gene in different cell types impaired by CF pathology. Across all cells, the CFTR locus is organized into an invariant topologically associated domain (TAD) established by the architectural proteins CCCTC-binding factor (CTCF) and cohesin complex. Additional insulator elements within the TAD also recruit these factors. Although the CFTR promoter is required for basal levels of expression, cis-regulatory elements (CREs) in intergenic and intronic regions are crucial for cell-specific and temporal coordination of CFTR transcription. These CREs are recruited to the promoter through chromatin looping mechanisms and enhance cell-type-specific expression. These features of the CFTR locus should be considered when designing gene-editing approaches, since failure to recognize their importance may disrupt gene expression and reduce the efficacy of therapies.

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 Spatial organization of the transcriptional regulatory network of Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Dong-Qing Sun ◽  
Liu Tian ◽  
Bin-Guang Ma
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Regulatory Network ◽  
Spatial Organization ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
3D Structure ◽  
Three Dimensional ◽  
3D Genome ◽  
Transcriptional Regulatory ◽  
Four Levels

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.

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

scholarly journals ClusterMap: multi-scale clustering analysis of spatial gene expression

2021 ◽  
Author(s):  
Yichun He ◽  
Xin Tang ◽  
Jiahao Huang ◽  
Haowen Zhou ◽  
Kevin Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dimensional Space ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Point Pattern Analysis ◽  
Point Pattern ◽  
Computational Framework ◽  
Spatially Resolved ◽  
Tissue Organization

AbstractQuantifying RNAs in their spatial context is crucial to understanding gene expression and regulation in complex tissues. In situ transcriptomic methods generate spatially resolved RNA profiles in intact tissues. However, there is a lack of a unified computational framework for integrative analysis of in situ transcriptomic data. Here, we present an unsupervised and annotation-free framework, termed ClusterMap, which incorporates physical proximity and gene identity of RNAs, formulates the task as a point pattern analysis problem, and thus defines biologically meaningful structures and groups. Specifically, ClusterMap precisely clusters RNAs into subcellular structures, cell bodies, and tissue regions in both two- and three-dimensional space, and consistently performs on diverse tissue types, including mouse brain, placenta, gut, and human cardiac organoids. We demonstrate ClusterMap to be broadly applicable to various in situ transcriptomic measurements to uncover gene expression patterns, cell-cell interactions, and tissue organization principles from high-dimensional transcriptomic images.

scholarly journals The three-dimensional landscape of chromatin accessibility in Alzheimer’s disease

2021 ◽  
Author(s):  
Jaroslav Bendl ◽  
Mads E. Hauberg ◽  
Kiran Girdhar ◽  
Eunju Im ◽  
James M. Vicari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
3D Structure ◽  
Three Dimensional ◽  
Superior Temporal Gyrus ◽  
Brain Regions ◽  
Chromatin Accessibility ◽  
Regulatory Sequences ◽  
3D Genome

AbstractMuch is still unknown about the neurobiology of Alzheimer’s disease (AD). To better understand AD, we generated 636 ATAC-seq libraries from cases and controls to construct detailed genomewide chromatin accessibility maps of neurons and non-neurons from two AD-affected brain regions, the entorhinal cortex and superior temporal gyrus. By analyzing a total of 19.6 billion read pairs, we expanded the known repertoire of regulatory sequences in the human brain. Multi-omic data integration associated global patterns of chromatin accessibility with gene expression and identified cell-specific enhancer-promoter interactions. Using inter-individual variation in chromatin accessibility, we define cis-regulatory domains capturing the 3D structure of the genome. Multifaceted analyses uncovered disease associated perturbations impacting chromatin accessibility, transcription factor regulatory networks and the 3D genome, and implicated transcriptional dysregulation in AD. Overall, we applied a systematic approach to understand the role of the 3D genome in AD and to illuminate novel disease biology that can advance diagnosis and therapy.

scholarly journals The Prospective Study of Epigenetic Regulatory Profiles in Sport and Exercise Monitored Through Chromosome Conformation Signatures

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 905
Author(s):  
Elliott C. R. Hall ◽  
Christopher Murgatroyd ◽  
Georgina K. Stebbings ◽  
Brian Cunniffe ◽  
Lee Harle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dimensional Space ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Medical Intervention ◽  
Gene Expression Patterns ◽  
Chromosome Conformation ◽  
Exercise Adaptation ◽  
Technological Advances ◽  
Sport And Exercise

The integration of genetic and environmental factors that regulate the gene expression patterns associated with exercise adaptation is mediated by epigenetic mechanisms. The organisation of the human genome within three-dimensional space, known as chromosome conformation, has recently been shown as a dynamic epigenetic regulator of gene expression, facilitating the interaction of distal genomic regions due to tight and regulated packaging of chromosomes in the cell nucleus. Technological advances in the study of chromosome conformation mean a new class of biomarker—the chromosome conformation signature (CCS)—can identify chromosomal interactions across several genomic loci as a collective marker of an epigenomic state. Investigative use of CCSs in biological and medical research shows promise in identifying the likelihood that a disease state is present or absent, as well as an ability to prospectively stratify individuals according to their likely response to medical intervention. The association of CCSs with gene expression patterns suggests that there are likely to be CCSs that respond, or regulate the response, to exercise and related stimuli. The present review provides a contextual background to CCS research and a theoretical framework discussing the potential uses of this novel epigenomic biomarker within sport and exercise science and medicine.

Syndecan-1 modulates the invasive potential of endometrioma via TGF-β signalling in a subgroup of women with endometriosis

2020 ◽  
Vol 35 (10) ◽  
pp. 2280-2293 ◽  
Author(s):  
Sakthivignesh Ponandai-Srinivasan ◽  
Merli Saare ◽  
Nageswara Rao Boggavarapu ◽  
Caroline Frisendahl ◽  
Sophia Ehrström ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Gene Silencing ◽  
Three Dimensional ◽  
Gene Clustering ◽  
Ovarian Endometriosis ◽  
Tgf Β1 ◽  
3D Spheroids

Abstract STUDY QUESTION What is the physiological role of transforming growth factor-beta (TGF-β1) and syndecans (SDC1, SDC4) in endometriotic cells in women with endometriosis? SUMMARY ANSWER We observed an abnormal, pro-invasive phenotype in a subgroup of samples with ovarian endometriosis, which was reversed by combining gene silencing of SDC1 with the TGF-β1 treatment. WHAT IS KNOWN ALREADY Women with endometriosis express high levels of TGF-β1 and the proteoglycan co-receptors SDC1 and SDC4 within endometriotic cysts. However, how SDC1 and SDC4 expression is regulated by TGF-β1 and the physiological significance of the high expression in endometriotic cysts remains unknown as does the potential role in disease severity. STUDY DESIGN, SIZE, DURATION We utilized a pre-validated panel of stem- and cancer cell-associated markers on endometriotic tissue (n = 15) to stratify subgroups of women with endometriosis. Furthermore, CD90+CD73+CD105+ (SC+) endometriotic stromal cells from these patient subgroups were explored for their invasive behaviour in vitro by transient gene inhibition of SDC1 or SDC4, both in the presence or absence of TGF-β1 treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS Endometriotic cyst biopsies (n = 15) were obtained from women diagnosed with ovarian endometriosis (ASRM Stage III–IV). Gene expression variability was assessed on tissue samples by applying gene clustering tools for the dataset generated from the pre-validated panel of markers. Three-dimensional (3D) spheroids from endometriotic SC+ were treated in vitro with increasing doses of TGF-β1 or the TGFBRI/II inhibitor Ly2109761 and assessed for SDC1, SDC4 expression and in vitro 3D-spheroid invasion. Transcriptomic signatures from the invaded 3D spheroids were evaluated upon combining transient gene silencing of SDC1 or SDC4, both in presence or absence of TGF-β1 treatment. Furthermore, nanoscale changes on the surface of endometriotic cells were analysed after treatment with TGF-β1 or TGFBRI/II inhibitor using atomic force microscopy. MAIN RESULTS AND THE ROLE OF CHANCE Gene clustering analysis revealed that endometriotic tissues displayed variability in their gene expression patterns; a small subgroup of samples (2/15, Endo-hi) exhibited high levels of SDC1, SDC4 and molecules involved in TGF-β signalling (TGF-β1, ESR1, CTNNB1, SNAI1, BMI1). The remaining endometriotic samples (Endo-lo) showed a uniform, low gene expression profile. Three-dimensional spheroids derived from Endo-hi SC+ but not Endo-lo SC+ samples showed an aberrant expression of SDC1 and exhibited enhanced 3D-spheroid invasion in vitro, upon rhTGF-β1 treatment. However, this abnormal, pro-invasive response of Endo-hi SC+ was reversed upon gene silencing of SDC1 with the TGF-β1 treatment. Interestingly, transcriptomic signatures of 3D spheroids silenced for SDC1 and consecutively treated with TGF-β1, showed a down-regulation of cancer-associated pathways such as WNT and GPCR signalling. LARGE SCALE DATA Transcriptomic data were deposited in NCBI’s Gene Expression Omnibus (GEO) and could be retrieved using GEO series accession number: GSE135122. LIMITATIONS, REASONS FOR CAUTION It is estimated that about 2.5% of endometriosis patients have a potential risk for developing ovarian cancer later in life. It is possible that the pro-oncogenic molecular changes observed in this cohort of endometriotic samples may not correlate with clinical occurrence of ovarian cancer later in life, thus a validation will be required. WIDER IMPLICATIONS OF THE FINDINGS This study emphasizes the importance of interactions between syndecans and TGF-β1 in the pathophysiology of endometriosis. We believe that this knowledge could be important in order to better understand endometriosis-associated complications such as ovarian cancer or infertility. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Cancerfonden (CAN 2016/696), Radiumhemmets Forskningsfonder (Project no. 154143 and 184033), EU MSCA-RISE-2015 project MOMENDO (691058), Estonian Ministry of Education and Research (IUT34-16), Enterprise Estonia (EU48695) and Karolinska Institute. Authors do not have any conflict of interest.

scholarly journals ОСОБЛИВОСТІ 3D МОДЕЛЮВАННЯ СТРУКТУРИ ТРИКОТАЖУ У МАКСИМАЛЬНО РОЗТЯГНУТОМУ СТАНІ

2021 ◽  
Vol 150 (5) ◽  
pp. 31-45
Author(s):  
Т. В. Єліна ◽  
Л. Є. Галавська ◽  
Д. Мікучіонене ◽  
Р. Мілашіус ◽  
В. І. Безсмертна
Keyword(s):  
Geometric Modeling ◽  
Tensile Deformation ◽  
Dimensional Space ◽  
3D Structure ◽  
Three Dimensional ◽  
3D Models ◽  
Structure Parameters ◽  
Loop Model ◽  
Loop Structure ◽  
Uniaxial Stretching

The  study  aims  at  the  development  mathematical  basics  for  software  for  automated construction of three-dimensional geometric models of knitwear in the most stretched state due to uniaxial stretching along the wale or course direction. Methodology.  The  research  methods  of  theoretical  analysis,  spline  theory,  methods  of  three-dimensional geometric modeling and parameterization, computer graphics tools, programming tools were used. Findings. During the research, it was assumed that in the maximally stretched state, the tangent to the centerline of the loop at the interlacing point is located at an angle of 45º to the vertical line oriented along the  wale  direction.  Mathematical  expressions  are  proposed  for  determining  the  co-ordinates  of  the characteristic points of the loop in three-dimensional space. An algorithm and its software implementation have been developed as a separate module of the Structure 3D program, designed to create models of knitwear in a stretched state. To verify the algorithm, samples of weft knitted fabrics were made with a 8th gauge flat-bed knitting machine of para-aramid and high-molecular polyethylene threads of linear density 58.8x2 tex and 44x3 tex, respectively. The parameters of the loop structure of the samples in dry-relaxed state and under maximum uniaxial stretching along the wale and the course directions. Tensile testing of specimens was performed on the machine KaoTieh KT-7010AZ. The maximum stress state of the samples was recorded using a Micro Capture Pro microscope to further determine the changes of the loop structure parameters under the action of tensile deformation. The obtained values of the the loop structure parameters of the samples were used as input data for the construction of three-dimensional models. The deviation of the value of the length of the spline representing the centerline of the thread in the loop model from the length of the thread in the loop obtained during the analysis of the samples does not exceed 5%. Scientific novelty. An algorithm for the automated construction of 3D models of knitted structures, undergoing maximum deformations coursed by uniaxial tension along the wales or course directions, has been developed. Practical value. A separate module of the 3D Structure program has been created for the automated construction of a knitted loop undergoing maximal stretching under has been developed.

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