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 ◽  
...  

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.

2011 ◽  
Vol 50 ◽  
pp. 19-42 ◽  
Author(s):  
Elie Dassa

In recent years, our understanding of the functioning of ABC (ATP-binding cassette) systems has been boosted by the combination of biochemical and structural approaches. However, the origin and the distribution of ABC proteins among living organisms are difficult to understand in a phylogenetic perspective, because it is hard to discriminate orthology and paralogy, due to the existence of horizontal gene transfer. In this chapter, I present an update of the classification of ABC systems and discuss a hypothetical scenario of their evolution. The hypothetical presence of ABC ATPases in the last common ancestor of modern organisms is discussed, as well as the additional possibility that ABC systems might have been transmitted to eukaryotes, after the two endosymbiosis events that led to the constitution of eukaryotic organelles. I update the functional information of selected ABC systems and introduce new families of ABC proteins that have been included recently into this vast superfamily, thanks to the availability of high-resolution three-dimensional structures.


2021 ◽  
Author(s):  
Ruoyu Wang ◽  
Joo-Hyung Lee ◽  
Feng Xiong ◽  
Jieun Kim ◽  
Lana Al Hasani ◽  
...  

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.


2009 ◽  
Vol 364 (1527) ◽  
pp. 2177-2185 ◽  
Author(s):  
James A. Lake ◽  
Ryan G. Skophammer ◽  
Craig W. Herbold ◽  
Jacqueline A. Servin

A rooted tree of life provides a framework to answer central questions about the evolution of life. Here we review progress on rooting the tree of life and introduce a new root of life obtained through the analysis of indels, insertions and deletions, found within paralogous gene sets. Through the analysis of indels in eight paralogous gene sets, the root is localized to the branch between the clade consisting of the Actinobacteria and the double-membrane (Gram-negative) prokaryotes and one consisting of the archaebacteria and the firmicutes. This root provides a new perspective on the habitats of early life, including the evolution of methanogenesis, membranes and hyperthermophily, and the speciation of major prokaryotic taxa. Our analyses exclude methanogenesis as a primitive metabolism, in contrast to previous findings. They parsimoniously imply that the ether archaebacterial lipids are not primitive and that the cenancestral prokaryotic population consisted of organisms enclosed by a single, ester-linked lipid membrane, covered by a peptidoglycan layer. These results explain the similarities previously noted by others between the lipid synthesis pathways in eubacteria and archaebacteria. The new root also implies that the last common ancestor was not hyperthermophilic, although moderate thermophily cannot be excluded.


2017 ◽  
Author(s):  
Stephanie L. Battle ◽  
Naresh Doni Jayavelu ◽  
Robert N. Azad ◽  
Jennifer Hesson ◽  
Faria N. Ahmed ◽  
...  

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.


2016 ◽  
Vol 3 (9) ◽  
pp. 160283 ◽  
Author(s):  
Yonas I. Tekle ◽  
Jessica R. Williams

The cytoskeleton is the hallmark of eukaryotic evolution. The molecular and architectural aspects of the cytoskeleton have been playing a prominent role in our understanding of the origin and evolution of eukaryotes. In this study, we seek to investigate the cytoskeleton architecture and its evolutionary significance in understudied amoeboid lineages belonging to Amoebozoa. These amoebae primarily use cytoplasmic extensions supported by the cytoskeleton to perform important cellular processes such as movement and feeding. Amoeboid structure has important taxonomic significance, but, owing to techniques used, its potential significance in understanding diversity of the group has been seriously compromised, leading to an under-appreciation of its value. Here, we used immunocytochemistry and confocal microscopy to study the architecture of microtubules (MTs) and F-actin in diverse groups of amoebae. Our results demonstrate that all Amoebozoa examined are characterized by a complex cytoskeletal array, unlike what has been previously thought to exist. Our results not only conclusively demonstrate that all amoebozoans possess complex cytoplasmic MTs, but also provide, for the first time, a potential synapomorphy for the molecularly defined Amoebozoa clade. Based on this evidence, the last common ancestor of amoebozoans is hypothesized to have had a complex interwoven MT architecture limited within the granular cell body. We also generate several cytoskeleton characters related to MT and F-actin, which are found to be robust for defining groups in deep and shallow nodes of Amoebozoa.


2020 ◽  
Vol 48 (W1) ◽  
pp. W170-W176
Author(s):  
Michal Wlasnowolski ◽  
Michal Sadowski ◽  
Tymon Czarnota ◽  
Karolina Jodkowska ◽  
Przemyslaw Szalaj ◽  
...  

Abstract Structural variants (SVs) that alter DNA sequence emerge as a driving force involved in the reorganisation of DNA spatial folding, thus affecting gene transcription. In this work, we describe an improved version of our integrated web service for structural modeling of three-dimensional genome (3D-GNOME), which now incorporates all types of SVs to model changes to the reference 3D conformation of chromatin. In 3D-GNOME 2.0, the default reference 3D genome structure is generated using ChIA-PET data from the GM12878 cell line and SVs data are sourced from the population-scale catalogue of SVs identified by the 1000 Genomes Consortium. However, users may also submit their own structural data to set a customized reference genome structure, and/or a custom input list of SVs. 3D-GNOME 2.0 provides novel tools to inspect, visualize and compare 3D models for regions that differ in terms of their linear genomic sequence. Contact diagrams are displayed to compare the reference 3D structure with the one altered by SVs. In our opinion, 3D-GNOME 2.0 is a unique online tool for modeling and analyzing conformational changes to the human genome induced by SVs across populations. It can be freely accessed at https://3dgnome.cent.uw.edu.pl/.


2021 ◽  
Vol 12 ◽  
Author(s):  
Alessandro Bertero

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.


2020 ◽  
Author(s):  
Qian Chen ◽  
Fengling Chen ◽  
Ruiting Wang ◽  
Minglei Shi ◽  
Antony K. Chen ◽  
...  

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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Roser Vilarrasa-Blasi ◽  
Paula Soler-Vila ◽  
Núria Verdaguer-Dot ◽  
Núria Russiñol ◽  
Marco Di Stefano ◽  
...  

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.


2018 ◽  
Vol 15 (145) ◽  
pp. 20180205 ◽  
Author(s):  
Matthew C. O'Neill ◽  
Brigitte Demes ◽  
Nathan E. Thompson ◽  
Brian R. Umberger

Humans are unique among apes and other primates in the musculoskeletal design of their lower back and pelvis. While the last common ancestor of the Pan–Homo lineages has long been thought to be ‘African ape-like’, including in its lower back and ilia design, recent descriptions of early hominin and Miocene ape fossils have led to the proposal that its lower back and ilia were more similar to those of some Old World monkeys, such as macaques. Here, we compared three-dimensional kinematics of the pelvis and hind/lower limbs of bipedal macaques, chimpanzees and humans walking at similar dimensionless speeds to test the effects of lower back and ilia design on gait. Our results indicate that locomotor kinematics of bipedal macaques and chimpanzees are remarkably similar, with both species exhibiting greater pelvis motion and more flexed, abducted hind limbs than humans during walking. Some differences between macaques and chimpanzees in pelvis tilt and hip abduction were noted, but they were small in magnitude; larger differences were observed in ankle flexion. Our results suggest that if Pan and Homo diverged from a common ancestor whose lower back and ilia were either ‘African ape-like’ or more ‘Old World monkey-like’, at its origin, the hominin walking stride likely involved distinct (i.e. non-human-like) pelvis motion on flexed, abducted hind limbs.


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