scholarly journals SARS-CoV-2 Restructures the Host Chromatin Architecture

2021 ◽  
Author(s):  
Ruoyu Wang ◽  
Joo-Hyung Lee ◽  
Feng Xiong ◽  
Jieun Kim ◽  
Lana Al Hasani ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Host Cells ◽  
Interferon Response ◽  
Genome Architecture ◽  
3D Genome ◽  
Chromatin Architecture ◽  
Severe Infections ◽  
Global Reduction ◽  
Host Chromatin

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.

scholarly journals Three-dimensional organization of chromatin associated RNAs and their role in chromatin architecture in human cells

2021 ◽  
Author(s):  
Riccardo Calandrelli ◽  
Xingzhao Wen ◽  
Tri C. Nguyen ◽  
Chien-Ju Chen ◽  
Zhijie Qi ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Chromatin Loops ◽  
3D Genome ◽  
Vital Component ◽  
Genome Interactions ◽  
Global Reduction

Chromatin-associated RNA (caRNA) is a vital component of the interphase nucleus; yet its distribution and role in the 3D genome organization remain poorly understood. Here, we map caRNA's spatial distribution on the 3D genome in human embryonic stem cells, fibroblasts, and myelogenous leukemia cells. We find that the relative abundance of trans-acting caRNA on DNA reflects the 3D compartmentalization, and the caRNA's sequence is predictive of its spatial localization. We observe localized caRNA-genome interactions that span several hundred kilobases to several megabases. These caRNA domains correlate with chromatin loops and enhancer-promoter interactions. Global reduction of caRNA abundance increases the number of chromatin loops and strengths, which could be reversed by suppression of caRNA's electrostatic interactions. These results indicate that caRNA regulates chromatin looping, at least in part through RNA's electrostatic interactions.

scholarly journals Epigenomic and 3D genome architecture in naïve and primed human embryonic stem cell states

2017 ◽  
Author(s):  
Stephanie L. Battle ◽  
Naresh Doni Jayavelu ◽  
Robert N. Azad ◽  
Jennifer Hesson ◽  
Faria N. Ahmed ◽  
...  
Keyword(s):  
Human Embryonic Stem Cell ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Genome Architecture ◽  
Open Chromatin ◽  
Substantial Portion ◽  
3D Genome ◽  
Mammalian Embryogenesis ◽  
Post Implantation ◽  
Epigenomic Reprogramming

ABSTRACTDuring mammalian embryogenesis changes in morphology and gene expression are concurrent with epigenomic reprogramming. Using human embryonic stem cells representing the pre-implantation blastocyst (naïve) and post-implantation epiblast (primed), our data demonstrate that a substantial portion of known human enhancers are pre-marked by H3K4me1 in naïve cells, providing an enhanced open chromatin state in naïve pluripotency. The naïve enhancer repertoire occupies nine percent of the genome, three times that of primed cells, and can exist in broad chromatin domains over fifty kilobases. Enhancer chromatin states are largely poised. Seventy-seven percent of naïve enhancers are decommissioned in a stepwise manner as cells become primed. While primed topological associated domains are unaltered upon differentiation, naïve domains expand across primed boundaries, impacting three dimensional genome architecture. Differential topological associated domain edges coincide with naïve H3K4me1 enrichment. Our results suggest that naïve-derived cells have a chromatin landscape reflective of early embryogenesis.

scholarly journals Understanding 3D Genome Organization and Its Effect on Transcriptional Gene Regulation Under Environmental Stress in Plant: A Chromatin Perspective

2021 ◽  
Vol 9 ◽  
Author(s):  
Suresh Kumar ◽  
Simardeep Kaur ◽  
Karishma Seem ◽  
Santosh Kumar ◽  
Trilochan Mohapatra
Keyword(s):  
Gene Expression ◽  
Environmental Stress ◽  
Genome Organization ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Chromatin Architecture ◽  
Capture Techniques

The genome of a eukaryotic organism is comprised of a supra-molecular complex of chromatin fibers and intricately folded three-dimensional (3D) structures. Chromosomal interactions and topological changes in response to the developmental and/or environmental stimuli affect gene expression. Chromatin architecture plays important roles in DNA replication, gene expression, and genome integrity. Higher-order chromatin organizations like chromosome territories (CTs), A/B compartments, topologically associating domains (TADs), and chromatin loops vary among cells, tissues, and species depending on the developmental stage and/or environmental conditions (4D genomics). Every chromosome occupies a separate territory in the interphase nucleus and forms the top layer of hierarchical structure (CTs) in most of the eukaryotes. While the A and B compartments are associated with active (euchromatic) and inactive (heterochromatic) chromatin, respectively, having well-defined genomic/epigenomic features, TADs are the structural units of chromatin. Chromatin architecture like TADs as well as the local interactions between promoter and regulatory elements correlates with the chromatin activity, which alters during environmental stresses due to relocalization of the architectural proteins. Moreover, chromatin looping brings the gene and regulatory elements in close proximity for interactions. The intricate relationship between nucleotide sequence and chromatin architecture requires a more comprehensive understanding to unravel the genome organization and genetic plasticity. During the last decade, advances in chromatin conformation capture techniques for unravelling 3D genome organizations have improved our understanding of genome biology. However, the recent advances, such as Hi-C and ChIA-PET, have substantially increased the resolution, throughput as well our interest in analysing genome organizations. The present review provides an overview of the historical and contemporary perspectives of chromosome conformation capture technologies, their applications in functional genomics, and the constraints in predicting 3D genome organization. We also discuss the future perspectives of understanding high-order chromatin organizations in deciphering transcriptional regulation of gene expression under environmental stress (4D genomics). These might help design the climate-smart crop to meet the ever-growing demands of food, feed, and fodder.

scholarly journals RNA Biogenesis Instructs Functional Inter-Chromosomal Genome Architecture

2021 ◽  
Vol 12 ◽  
Author(s):  
Alessandro Bertero
Keyword(s):  
Rna Polymerase Ii ◽  
Cardiac Myocyte ◽  
Three Dimensional ◽  
Mitotic Cell ◽  
Genome Architecture ◽  
3D Genome ◽  
Functional Relationships ◽  
Splicing Regulator ◽  
Rna Biogenesis ◽  
Chromatin Folding

Three-dimensional (3D) genome organization has emerged as an important layer of gene regulation in development and disease. The functional properties of chromatin folding within individual chromosomes (i.e., intra-chromosomal or in cis) have been studied extensively. On the other hand, interactions across different chromosomes (i.e., inter-chromosomal or in trans) have received less attention, being often regarded as background noise or technical artifacts. This viewpoint has been challenged by emerging evidence of functional relationships between specific trans chromatin interactions and epigenetic control, transcription, and splicing. Therefore, it is an intriguing possibility that the key processes involved in the biogenesis of RNAs may both shape and be in turn influenced by inter-chromosomal genome architecture. Here I present the rationale behind this hypothesis, and discuss a potential experimental framework aimed at its formal testing. I present a specific example in the cardiac myocyte, a well-studied post-mitotic cell whose development and response to stress are associated with marked rearrangements of chromatin topology both in cis and in trans. I argue that RNA polymerase II clusters (i.e., transcription factories) and foci of the cardiac-specific splicing regulator RBM20 (i.e., splicing factories) exemplify the existence of trans-interacting chromatin domains (TIDs) with important roles in cellular homeostasis. Overall, I propose that inter-molecular 3D proximity between co-regulated nucleic acids may be a pervasive functional mechanism in biology.

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

Science ◽  
2021 ◽  
Vol 372 (6545) ◽  
pp. 984-989
Author(s):  
Claire Hoencamp ◽  
Olga Dudchenko ◽  
Ahmed M. O. Elbatsh ◽  
Sumitabha Brahmachari ◽  
Jonne A. Raaijmakers ◽  
...  
Keyword(s):  
Human Genome ◽  
Physical Model ◽  
Common Ancestor ◽  
Three Dimensional ◽  
Tree Of Life ◽  
Genome Architecture ◽  
Last Common Ancestor ◽  
Eukaryotic Evolution ◽  
3D Genome ◽  
3D Genomics

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.

scholarly journals MyoD is a structure organizer of 3D genome architecture in muscle cells

2020 ◽  
Author(s):  
Qian Chen ◽  
Fengling Chen ◽  
Ruiting Wang ◽  
Minglei Shi ◽  
Antony K. Chen ◽  
...  
Keyword(s):  
Genome Organization ◽  
Three Dimensional ◽  
Muscle Cells ◽  
Cell Types ◽  
Linear Molecule ◽  
Basic Question ◽  
Genome Architecture ◽  
Cell Type ◽  
3D Genome ◽  
A Genome

AbstractThe genome is not a linear molecule of DNA randomly folded in the nucleus, but exists as an organized, three-dimensional (3D) dynamic architecture. Intriguingly, it is now clear that each cell type has a unique and characteristic 3D genome organization that functions in determining cell identity during development. A currently challenging basic question is how cell-type specific 3D genome structures are established during development. Herein, we analyzed 3D genome structures in primary myoblasts and myocytes from MyoD knockout (MKO) and wild type (WT) mice and discovered that MyoD, a pioneer transcription factor (TF), can function as a “genome organizer” that specifies the proper 3D genome architecture unique to muscle cell development. Importantly, we genetically demonstrate that H3K27ac is insufficient for establishing MyoD-induced chromatin loops in muscle cells. The establishment of MyoD’s “architectural role” should have profound impacts on advancing understanding of other pioneer transcription factors in orchestrating lineage specific 3D genome organization during development in a potentially very large number of cell types in diverse organisms.

scholarly journals Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Roser Vilarrasa-Blasi ◽  
Paula Soler-Vila ◽  
Núria Verdaguer-Dot ◽  
Núria Russiñol ◽  
Marco Di Stefano ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Three Dimensional ◽  
Lymphocytic Leukemia ◽  
Genome Architecture ◽  
B Cell Differentiation ◽  
3D Genome ◽  
Chromatin Activation ◽  
Genome Interactions

AbstractTo investigate the three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia and mantle cell lymphoma patients, here we integrate in situ Hi-C and nine additional omics layers. Beyond conventional active (A) and inactive (B) compartments, we uncover a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, 28% of the compartments change, mostly involving a widespread chromatin activation from naive to germinal center B cells and a reversal to the naive state upon further maturation into memory B cells. B cell neoplasms are characterized by both entity and subtype-specific alterations in 3D genome organization, including large chromatin blocks spanning key disease-specific genes. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.

scholarly journals Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution

2017 ◽  
Author(s):  
Wenxiu Ma ◽  
Ferhat Ay ◽  
Choli Lee ◽  
Gunhan Gulsoy ◽  
Xinxian Deng ◽  
...  
Keyword(s):  
High Resolution ◽  
High Throughput ◽  
Three Dimensional ◽  
Dnase I ◽  
Genome Architecture ◽  
Whole Genome ◽  
Fine Scale ◽  
3D Genome ◽  
Dna Capture ◽  
Global And Local

AbstractThe folding and three-dimensional (3D) organization of chromatin in the nucleus critically impacts genome function. The past decade has witnessed rapid advances in genomic tools for delineating 3D genome architecture. Among them, chromosome conformation capture (3C)-based methods such as Hi-C are the most widely used techniques for mapping chromatin interactions. However, traditional Hi-C protocols rely on restriction enzymes (REs) to fragment chromatin and are therefore limited in resolution. We recently developed DNase Hi-C for mapping 3D genome organization, which uses DNase I for chromatin fragmentation. DNase Hi-C overcomes RE-related limitations associated with traditional Hi-C methods, leading to improved methodological resolution. Furthermore, combining this method with DNA capture technology provides a high-throughput approach (targeted DNase Hi-C) that allows for mapping fine-scale chromatin architecture at exceptionally high resolution. Hence, targeted DNase Hi-C will be valuable for delineating the physical landscapes of cis-regulatory networks that control gene expression and for characterizing phenotype-associated chromatin 3D signatures. Here, we provide a detailed description of method design and step-by-step working protocols for these two methods.HighlightsDNase Hi-C, a method for comprehensive mapping of chromatin contacts on a whole-genome scale, is based on random chromatin fragmentation by DNase I digestion instead of sequence-specific restriction enzyme (RE) digestion.Targeted DNase Hi-C, which combines DNase Hi-C with DNA capture technology, is a high-throughput method for mapping fine-scale chromatin architecture of genomic loci of interest at a resolution comparable to that of genomic annotations of functional elements.DNase Hi-C and targeted DNase Hi-C provide the first high-throughput way to overcome the RE-digestion-associated resolution limit of 3C-based methods.Step-by-step whole-genome and targeted DNase Hi-C protocols for mapping global and local 3D genome architecture, respectively, are described.

Practical electron tomography

1995 ◽  
Vol 53 ◽  
pp. 742-743
Author(s):  
C.L. Woodcock
Keyword(s):  
Electron Tomography ◽  
Tomographic Reconstruction ◽  
Three Dimensional ◽  
3D Shape ◽  
Computational Resources ◽  
Shape Of Particles

Despite the potential of the technique, electron tomography has yet to be widely used by biologists. This is in part related to the rather daunting list of equipment and expertise that are required. Thanks to continuing advances in theory and instrumentation, tomography is now more feasible for the non-specialist. One barrier that has essentially disappeared is the expense of computational resources. In view of this progress, it is time to give more attention to practical issues that need to be considered when embarking on a tomographic project. The following recommendations and comments are derived from experience gained during two long-term collaborative projects.Tomographic reconstruction results in a three dimensional description of an individual EM specimen, most commonly a section, and is therefore applicable to problems in which ultrastructural details within the thickness of the specimen are obscured in single micrographs. Information that can be recovered using tomography includes the 3D shape of particles, and the arrangement and dispostion of overlapping fibrous and membranous structures.

Custom Presurgical Planning for Midfacial Reconstruction

2020 ◽  
Vol 36 (06) ◽  
pp. 696-702
Author(s):  
Nolan B. Seim ◽  
Enver Ozer ◽  
Sasha Valentin ◽  
Amit Agrawal ◽  
Mead VanPutten ◽  
...  
Keyword(s):  
Multidisciplinary Approach ◽  
Functional Performance ◽  
Three Dimensional ◽  
Free Tissue Transfer ◽  
Long Term Effects ◽  
Presurgical Planning ◽  
Dental Rehabilitation ◽  
Midface Reconstruction ◽  
Reconstructive Algorithm

AbstractResection and reconstruction of midface involve complex ablative and reconstructive tools in head and oncology and maxillofacial prosthodontics. This region is extraordinarily important for long-term aesthetic and functional performance. From a reconstructive standpoint, this region has always been known to present challenges to a reconstructive surgeon due to the complex three-dimensional anatomy, the variable defects created, combination of the medical and dental functionalities, and the distance from reliable donor vessels for free tissue transfer. Another challenge one faces is the unique features of each individual resection defect as well as individual patient factors making each preoperative planning session and reconstruction unique. Understanding the long-term effects on speech, swallowing, and vision, one should routinely utilize a multidisciplinary approach to resection and reconstruction, including head and neck reconstructive surgeons, prosthodontists, speech language pathologists, oculoplastic surgeons, dentists, and/or craniofacial teams as indicated and with each practice pattern. With this in mind, we present our planning and reconstructive algorithm in midface reconstruction, including a dedicated focus on dental rehabilitation via custom presurgical planning.

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