scholarly journals Reorganization of the 3D chromatin architecture of rice genomes during heat stress

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhe Liang ◽  
Qian Zhang ◽  
Changmian Ji ◽  
Guihua Hu ◽  
Pingxian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Spatial Organization ◽  
Environmental Changes ◽  
Three Dimensional ◽  
Chromatin Accessibility ◽  
Nuclear Dynamics ◽  
Functional Changes ◽  
Chromatin Architecture ◽  
Topologically Associated Domains

Abstract Background The three-dimensional spatial organization of the genome plays important roles in chromatin accessibility and gene expression in multiple biological processes and has been reported to be altered in response to environmental stress. However, the functional changes in spatial genome organization during environmental changes in crop plants are poorly understood. Results Here we perform Hi-C, ATAC-seq, and RNA-seq in two agronomically important rice cultivars, Nipponbare (Nip; Japonica) and 93-11 (Indica), to report a comprehensive profile of nuclear dynamics during heat stress (HS). We show that heat stress affects different levels of chromosome organization, including A/B compartment transition, increase in the size of topologically associated domains, and loss of short-range interactions. The chromatin architectural changes were associated with chromatin accessibility and gene expression changes. Comparative analysis revealed that 93-11 exhibited more dynamic gene expression and chromatin accessibility changes, including HS-related genes, consistent with observed higher HS tolerance in this cultivar. Conclusions Our data uncovered higher-order chromatin architecture as a new layer in understanding transcriptional regulation in response to heat stress in rice.

scholarly journals Senescence-activated enhancer landscape orchestrates the senescence-associated secretory phenotype in murine fibroblasts

2020 ◽  
Vol 48 (19) ◽  
pp. 10909-10923
Author(s):  
Yiting Guan ◽  
Chao Zhang ◽  
Guoliang Lyu ◽  
Xiaoke Huang ◽  
Xuebin Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Replicative Senescence ◽  
Three Dimensional ◽  
Enhancer Activity ◽  
Chromatin Architecture ◽  
Enhancer Binding Protein ◽  
Topologically Associated Domains ◽  
Secretory Phenotype ◽  
Three Dimensional Configuration ◽  
Underlying Mechanisms

Abstract The three-dimensional configuration of the chromatin architecture is known to be crucial for alterations in the transcriptional network; however, the underlying mechanisms of epigenetic control of senescence-related gene expression by modulating the chromatin architecture remain unknown. Here, we demonstrate frequent chromosomal compartment switching during mouse embryonic fibroblasts (MEFs) replicative senescence as characterized by senescence-inactivated (SIAEs) and -activated enhancers (SAEs) in topologically associated domains (TADs). Mechanistically, SAEs are closely correlated with senescence-associated secretory phenotype (SASP) genes, which are a key transcriptional feature of an aging microenvironment that contributes to tumor progression, aging acceleration, and immunoinflammatory responses. Moreover, SAEs can positively regulate robust changes in SASP expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is capable of enhancing SAE activity, which accelerates the emergence of SAEs flanking SASPs and the secretion of downstream factors, contributing to the progression of senescence. Our results provide novel insight into the TAD-related control of SASP gene expression by revealing hierarchical roles of the chromatin architecture, transcription factors, and enhancer activity in the regulation of cellular senescence.

scholarly journals EPCO-31. EPIGENOMIC INTRATUMORAL HETEROGENEITY OF GLIOBLASTOMA IN THREE-DIMENSIONAL SPACE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii76-ii76
Author(s):  
Radhika Mathur ◽  
Sriranga Iyyanki ◽  
Stephanie Hilz ◽  
Chibo Hong ◽  
Joanna Phillips ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Spatial Location ◽  
Therapy Resistance ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Intratumoral Heterogeneity ◽  
Tumor Evolution ◽  
Open Chromatin

Abstract Treatment failure in glioblastoma is often attributed to intratumoral heterogeneity (ITH), which fosters tumor evolution and generation of therapy-resistant clones. While ITH in glioblastoma has been well-characterized at the genomic and transcriptomic levels, the extent of ITH at the epigenomic level and its biological and clinical significance are not well understood. In collaboration with neurosurgeons, neuropathologists, and biomedical imaging experts, we have established a novel topographical approach towards characterizing epigenomic ITH in three-dimensional (3-D) space. We utilize pre-operative MRI scans to define tumor volume and then utilize 3-D surgical neuro-navigation to intra-operatively acquire 10+ samples representing maximal anatomical diversity. The precise spatial location of each sample is mapped by 3-D coordinates, enabling tumors to be visualized in 360-degrees and providing unprecedented insight into their spatial organization and patterning. For each sample, we conduct assay for transposase-accessible chromatin using sequencing (ATAC-Seq), which provides information on the genomic locations of open chromatin, DNA-binding proteins, and individual nucleosomes at nucleotide resolution. We additionally conduct whole-exome sequencing and RNA sequencing for each spatially mapped sample. Integrative analysis of these datasets reveals distinct patterns of chromatin accessibility within glioblastoma tumors, as well as their associations with genetically defined clonal expansions. Our analysis further reveals how differences in chromatin accessibility within tumors reflect underlying transcription factor activity at gene regulatory elements, including both promoters and enhancers, and drive expression of particular gene expression sets, including neuronal and immune programs. Collectively, this work provides the most comprehensive characterization of epigenomic ITH to date, establishing its importance for driving tumor evolution and therapy resistance in glioblastoma. As a resource for further investigation, we have provided our datasets on an interactive data sharing platform – The 3D Glioma Atlas – that enables 360-degree visualization of both genomic and epigenomic ITH.

scholarly journals Spatial organization of transcript elongation and splicing kinetics

2021 ◽  
Author(s):  
Alyssa D. Casill ◽  
Adam J. Haimowitz ◽  
Brian Kosmyna ◽  
Charles C. Query ◽  
Kenny Ye ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Spatial Organization ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Multiple Control ◽  
Pol Ii ◽  
Topologically Associated Domains ◽  
Transcript Elongation ◽  
Kinetics Of

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.

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 Spatial organization of different sigma factor activities and c-di-GMP signalling within the three-dimensional landscape of a bacterial biofilm

Open Biology ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 180066 ◽  
Author(s):  
Gisela Klauck ◽  
Diego O. Serra ◽  
Alexandra Possling ◽  
Regine Hengge
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Stationary Phase ◽  
Sigma Factor ◽  
Spatial Organization ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Biomechanical Properties ◽  
Ribosomal Gene ◽  
Bacterial Biofilm

Bacterial biofilms are large aggregates of cells embedded in an extracellular matrix of self-produced polymers. In macrocolony biofilms of Escherichia coli , this matrix is generated in the upper biofilm layer only and shows a surprisingly complex supracellular architecture. Stratified matrix production follows the vertical nutrient gradient and requires the stationary phase σ S (RpoS) subunit of RNA polymerase and the second messenger c-di-GMP. By visualizing global gene expression patterns with a newly designed fingerprint set of Gfp reporter fusions, our study reveals the spatial order of differential sigma factor activities, stringent control of ribosomal gene expression and c-di-GMP signalling in vertically cryosectioned macrocolony biofilms. Long-range physiological stratification shows a duplication of the growth-to-stationary phase pattern that integrates nutrient and oxygen gradients. In addition, distinct short-range heterogeneity occurs within specific biofilm strata and correlates with visually different zones of the refined matrix architecture. These results introduce a new conceptual framework for the control of biofilm formation and demonstrate that the intriguing extracellular matrix architecture, which determines the emergent physiological and biomechanical properties of biofilms, results from the spatial interplay of global gene regulation and microenvironmental conditions. Overall, mature bacterial macrocolony biofilms thus resemble the highly organized tissues of multicellular organisms.

scholarly journals Intranuclear trafficking of transcription factors: implications for biological control

2000 ◽  
Vol 113 (14) ◽  
pp. 2527-2533 ◽  
Author(s):  
G.S. Stein ◽  
A.J. van Wijnen ◽  
J.L. Stein ◽  
J.B. Lian ◽  
M. Montecino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Myelogenous Leukemia ◽  
Regulatory Factors ◽  
Acute Myelogenous ◽  
Gene Transcripts ◽  
Targeting Signals ◽  
Discrete Domains

The subnuclear organization of nucleic acids and cognate regulatory factors suggests that there are functional interrelationships between nuclear structure and gene expression. Nuclear proteins that are localized in discrete domains within the nucleus include the leukemia-associated acute myelogenous leukemia (AML) and promyelocytic leukemia (PML) factors, the SC-35 RNA-processing factors, nucleolar proteins and components of both transcriptional and DNA replication complexes. Mechanisms that control the spatial distribution of transcription factors within the three-dimensional context of the nucleus may involve the sorting of regulatory information, as well as contribute to the assembly and activity of sites that support gene expression. Molecular, cellular, genetic and biochemical approaches have identified distinct protein segments, termed intranuclear-targeting signals, that are responsible for directing regulatory factors to specific subnuclear sites. Gene rearrangements that remove or alter intranuclear-targeting signals are prevalent in leukemias and have been linked to altered localization of regulatory factors within the nucleus. These modifications in the intranuclear targeting of transcription factors might abrogate fidelity of gene expression in tumor cells by influencing the spatial organization and/or assembly of machineries involved in the synthesis and processing of gene transcripts.

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.

scholarly journals Three-dimensional organization of Drosophila melanogaster interphase nuclei. II. Chromosome spatial organization and gene regulation.

1987 ◽  
Vol 104 (6) ◽  
pp. 1471-1483 ◽  
Author(s):  
M Hochstrasser ◽  
J W Sedat
Keyword(s):  
Gene Regulation ◽  
Drosophila Melanogaster ◽  
Nuclear Envelope ◽  
Spatial Organization ◽  
Polytene Chromosomes ◽  
Three Dimensional ◽  
Nucleolar Organizer ◽  
Cell Types ◽  
Functional Changes ◽  
Specific Subset

In the preceding article we compared the general organization of polytene chromosomes in four different Drosophila melanogaster cell types. Here we describe experiments aimed at testing for a potential role of three-dimensional chromosome folding and positioning in modulating gene expression and examining specific chromosome interactions with different nuclear structures. By charting the configurations of salivary gland chromosomes as the cells undergo functional changes, it is shown that loci are not repositioned within the nucleus when the pattern of transcription changes. Heterologous loci show no evidence of specific physical interactions with one another in any of the cell types. However, a specific subset of chromosomal loci is attached to the nuclear envelope, and this subset is extremely similar in at least two tissues. In contrast, no specific interactions between any locus and the nucleolus are found, but the base of the X chromosome, containing the nucleolar organizer, is closely linked to this organelle. These results are used to evaluate models of gene regulation that involve the specific intranuclear positioning of gene sequences. Finally, data are presented on an unusual class of nuclear envelope structures, filled with large, electron-dense particles, that are usually associated with chromosomes.

scholarly journals Multi-level remodelling of chromatin underlying activation of human T cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naiara G. Bediaga ◽  
Hannah D. Coughlan ◽  
Timothy M. Johanson ◽  
Alexandra L. Garnham ◽  
Gaetano Naselli ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Chromatin Accessibility ◽  
Chromatin Architecture ◽  
Chromatin Interactions ◽  
Human T Cells ◽  
Multi Level

AbstractRemodelling of chromatin architecture is known to regulate gene expression and has been well characterized in cell lineage development but less so in response to cell perturbation. Activation of T cells, which triggers extensive changes in transcriptional programs, serves as an instructive model to elucidate how changes in chromatin architecture orchestrate gene expression in response to cell perturbation. To characterize coordinate changes at different levels of chromatin architecture, we analyzed chromatin accessibility, chromosome conformation and gene expression in activated human T cells. T cell activation was characterized by widespread changes in chromatin accessibility and interactions that were shared between activated CD4+ and CD8+ T cells, and with the formation of active regulatory regions associated with transcription factors relevant to T cell biology. Chromatin interactions that increased and decreased were coupled, respectively, with up- and down-regulation of corresponding target genes. Furthermore, activation was associated with disruption of long-range chromatin interactions and with partitioning of topologically associating domains (TADs) and remodelling of their TAD boundaries. Newly formed/strengthened TAD boundaries were associated with higher nucleosome occupancy and lower accessibility, linking changes in lower and higher order chromatin architecture. T cell activation exemplifies coordinate multi-level remodelling of chromatin underlying gene transcription.

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