scholarly journals Studying 3D genome evolution using genomic sequence

2019 ◽  
Author(s):  
Raphaël Mourad
Keyword(s):  
Genome Evolution ◽  
Genomic Sequence ◽  
Regulation Of Gene Expression ◽  
Replication Timing ◽  
Evolutionary Constraints ◽  
3D Genome ◽  
Chromatin Looping ◽  
Novel Approach ◽  
Evolutionary Studies ◽  
Ancestral Character Reconstruction

AbstractThe 3D genome is essential to numerous key processes such as the regulation of gene expression and the replication-timing program. In vertebrates, chromatin looping is often mediated by CTCF, and marked by CTCF motif pairs in convergent orientation. Comparative Hi-C recently revealed that chromatin looping evolves across species. However, Hi-C experiments are complex and costly, which currently limits their use for evolutionary studies over a large number of species. Here, we propose a novel approach to study the 3D genome evolution in vertebrates using the genomic sequence only, e.g. without the need for Hi-C data. The approach is simple and relies on comparing the distances between convergent and divergent CTCF motifs (ratio R). We show that R is a powerful statistic to detect CTCF looping encoded in the human genome sequence, thus reflecting strong evolutionary constraints encoded in DNA and associated with the 3D genome. When comparing vertebrate genomes, our results reveal that R which underlies CTCF looping and TAD organization evolves over time and suggest that ancestral character reconstruction can be used to infer R in ancestral genomes.

scholarly journals Studying 3D genome evolution using genomic sequence

2019 ◽  
Author(s):  
Raphaël Mourad
Keyword(s):  
Genome Evolution ◽  
High Throughput Sequencing ◽  
Genomic Sequence ◽  
Regulation Of Gene Expression ◽  
Replication Timing ◽  
Three Dimensions ◽  
Supplementary Information ◽  
3D Genome ◽  
Chromatin Looping ◽  
Novel Approach

Abstract Motivation The three dimensions (3D) genome is essential to numerous key processes such as the regulation of gene expression and the replication-timing program. In vertebrates, chromatin looping is often mediated by CTCF, and marked by CTCF motif pairs in convergent orientation. Comparative high-throughput sequencing technique (Hi-C) recently revealed that chromatin looping evolves across species. However, Hi-C experiments are complex and costly, which currently limits their use for evolutionary studies over a large number of species. Results Here, we propose a novel approach to study the 3D genome evolution in vertebrates using the genomic sequence only, e.g. without the need for Hi-C data. The approach is simple and relies on comparing the distances between convergent and divergent CTCF motifs by computing a ratio we named the 3D ratio or ‘3DR’. We show that 3DR is a powerful statistic to detect CTCF looping encoded in the human genome sequence, thus reflecting strong evolutionary constraints encoded in DNA and associated with the 3D genome. When comparing vertebrate genomes, our results reveal that 3DR which underlies CTCF looping and topologically associating domain organization evolves over time and suggest that ancestral character reconstruction can be used to infer 3DR in ancestral genomes. Availability and implementation The R code is available at https://github.com/morphos30/PhyloCTCFLooping. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Active Targeted Surveillance to Identify Sites of Emergence of Hantavirus

2019 ◽  
Vol 70 (3) ◽  
pp. 464-473 ◽  
Author(s):  
Won-Keun Kim ◽  
Jin Sun No ◽  
Daesang Lee ◽  
Jaehun Jung ◽  
Hayne Park ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Disease Risk ◽  
Hemorrhagic Fever ◽  
Epidemiological Surveillance ◽  
Likelihood Method ◽  
Comparative Genomic ◽  
Novel Approach ◽  
Epidemiological Surveys ◽  
Outbreak Areas ◽  
Complete Sequences

Abstract Background Endemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we were able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequences; finer granularity of rodent sampling reflects more precisely the circulation of strains. Methods Five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex polymerase chain reaction–based next-generation sequencing to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated using the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on the bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents. Results The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens, with HTNV circulating in rodents at suspected sites of patient infections. Conclusions This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will make it possible to identify infectious sources, perform disease risk assessment, and implement preparedness against vector-borne viruses.

scholarly journals A Multigraph model of the 3D genome

2021 ◽  
Author(s):  
Diana Makai ◽  
Andras Cseh ◽  
Adel Sepsi ◽  
Szabolcs Makai
Keyword(s):  
Information Needs ◽  
Dimensional Space ◽  
Decisive Role ◽  
Regulatory Elements ◽  
Sequence Information ◽  
Genomic Context ◽  
3D Genome ◽  
Flexible Polymer ◽  
Novel Approach ◽  
Contact Data

Spatial organisation of the genome has a fundamental effect on its biological functions. Chromatin-chromatin interactions and 3D spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts as a whole to environmental stimuli, the linear sequence information needs to be interpreted in 3-dimensional space. While recent advances in chromatin conformation capture technologies including Hi-C, considerably advanced our understanding of the genomes, defining the DNA, as it is organized in the cell nucleus is still a challenging task. 3D genome modelling needs to reflect the DNA as a flexible polymer, which can wind up to the fraction of its total length and greatly unwind and stretch to implement a multitude of functions. Here we propose a novel approach to model genomes as a multigraph based on Hi-C contact data. Multigraph-based 3D genome modelling of barley and rice revealed the well-known Rabl and Rosetta chromatin organizations, respectively, as well as other higher order structures. Our results shows that the well-established toolset of Graph theory is highly valuable in modelling large genomes in 3D.

scholarly journals RNAs as proximity labeling media for identifying nuclear speckle positions relative to the genome

2018 ◽  
Author(s):  
Weizhong Chen ◽  
Zhangming Yan ◽  
Simin Li ◽  
Norman Huang ◽  
Xuerui Huang ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Genomic Sequence ◽  
Single Cells ◽  
Regulation Of Gene Expression ◽  
Nuclear Genome ◽  
Fold Increase ◽  
Nuclear Speckles ◽  
Nuclear Speckle ◽  
Interaction Sites ◽  
Genomic Regions

AbstractNuclear speckles are interchromatin structures enriched in RNA splicing factors. Determining their relative positions with respect to the folded nuclear genome could provide critical information on co-and post-transcriptional regulation of gene expression. However, it remains challenging to identify which parts of the nuclear genome are in proximity to nuclear speckles, due to physical separation between nuclear speckle cores and chromatin. We hypothesized that noncoding RNAs including small nuclear RNAs, 7SK and Malat1, which accumulate at the periphery of nuclear speckles (nsaRNA,nuclearspeckleassociated RNA), may extend to sufficient proximity to the nuclear genome. Leveraging a transcriptome-genome interaction assay (MARGI), we identified nsaRNA-interacting genomic sequences, which exhibited clustering patterns (nsaPeaks) in the genome, suggesting existence of relatively stable interaction sites for nsaRNAs in nuclear genome. Posttranscriptional pre-mRNAs, which are known to be clustered to nuclear speckles, exhibited proximity to nsaPeaks but rarely to other genomic regions. Furthermore, CDK9 proteins that localize to the vicinity of nuclear speckles produced ChIP-seq peaks that overlapped with nsaPeaks. Our combined DNA FISH and immunofluorescence analysis in 182 single cells revealed a 3-fold increase in odds for nuclear speckles to localize near an nsaPeak than its neighboring genomic sequence. These data suggest a model that nsaRNAs locate in sufficient proximity to nuclear genome and leave identifiable genomic footprints, thus revealing the parts of genome proximal to nuclear speckles.

scholarly journals Repeat elements organize 3D genome structure and mediate transcription in the filamentous fungusEpichloë festucae

2018 ◽  
Author(s):  
David J Winter ◽  
Austen RD Ganley ◽  
Carolyn A Young ◽  
Ivan Liachko ◽  
Christopher L Schardl ◽  
...  
Keyword(s):  
Genome Structure ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Structural Features ◽  
Dimensional Structure ◽  
In Planta ◽  
Repeat Elements ◽  
Symbiotic Relationships ◽  
3D Genome ◽  
Transcriptional Changes

AbstractStructural features of genomes, including the three-dimensional arrangement of DNA in the nucleus, are increasingly seen as key contributors to the regulation of gene expression. However, studies on how genome structure and nuclear organization influence transcription have so far been limited to a handful of model species. This narrow focus limits our ability to draw general conclusions about the ways in which three-dimensional structures are encoded, and to integrate information from three-dimensional data to address a broader gamut of biological questions. Here, we generate a complete and gapless genome sequence for the filamentous fungus,Epichloë festucae. Coupling it with RNAseq and HiC data, we investigate how the structure of the genome contributes to the suite of transcriptional changes that anEpichloëspecies needs to maintain symbiotic relationships with its grass host. Our results reveal a unique “patchwork” genome, in which repeat-rich blocks of DNA with discrete boundaries are interspersed by gene-rich sequences. In contrast to other species, the three-dimensional structure of the genome is anchored by these repeat blocks, which act to isolate transcription in neighbouring gene-rich regions. Genes that are differentially expressed in planta are enriched near the boundaries of these repeat-rich blocks, suggesting that their three-dimensional orientation partly encodes and regulates the symbiotic relationship formed by this organism.

scholarly journals Replication Timing Becomes Intertwined with 3D Genome Organization

Cell ◽  
2019 ◽  
Vol 176 (4) ◽  
pp. 681-684 ◽  
Author(s):  
Jian Ma ◽  
Zhijun Duan
Keyword(s):  
Genome Organization ◽  
Replication Timing ◽  
3D Genome

Control of DNA replication timing in the 3D genome

2019 ◽  
Vol 20 (12) ◽  
pp. 721-737 ◽  
Author(s):  
Claire Marchal ◽  
Jiao Sima ◽  
David M. Gilbert
Keyword(s):  
Dna Replication ◽  
Replication Timing ◽  
3D Genome ◽  
Dna Replication Timing

scholarly journals Inhibition of coxsackievirus B3 and related enteroviruses by antiviral short interfering RNA pools produced using φ6 RNA-dependent RNA polymerase

2009 ◽  
Vol 90 (10) ◽  
pp. 2468-2473 ◽  
Author(s):  
Michaela Nygårdas ◽  
Tytti Vuorinen ◽  
Antti P. Aalto ◽  
Dennis H. Bamford ◽  
Veijo Hukkanen
Keyword(s):  
Rna Polymerase ◽  
Genomic Sequence ◽  
Coxsackievirus B3 ◽  
Human Enterovirus ◽  
Rna Dependent Rna Polymerase ◽  
Coxsackievirus B4 ◽  
Novel Approach ◽  
Experimental Therapies ◽  
Coxsackievirus A9 ◽  
Interfering Rna

Coxsackievirus B3 (CBV3) is a member of the human enterovirus B species and a common human pathogen. Even though much is known about the enteroviral life cycle, no specific drugs are available to treat enterovirus infections. RNA interference (RNAi) has evolved to be an important tool for antiviral experimental therapies and gene function studies. We describe here a novel approach for RNAi against CBVs by using a short interfering (siRNA) pool covering 3.5 kb of CBV3 genomic sequence. The RNA-dependent RNA polymerase (RdRP) of bacteriophage φ6 was used to synthesize long double-stranded RNA (dsRNA) from a cloned region (nt 3837–7399) of the CBV3 genome. The dsRNA was cleaved using Dicer, purified and introduced to cells by transfection. The siRNA pool synthesized using the φ6 RdRP (φ6–siRNAs) was considerably more effective than single-site siRNAs. The φ6–siRNA pool also inhibited replication of other enterovirus B species, such as coxsackievirus B4 and coxsackievirus A9.

scholarly journals Positive Regulation of Leptospira interrogans kdp Expression by KdpE as Demonstrated with a Novel β-Galactosidase Reporter in Leptospira biflexa

2012 ◽  
Vol 78 (16) ◽  
pp. 5699-5707 ◽  
Author(s):  
James Matsunaga ◽  
Mariana L. Coutinho
Keyword(s):  
Gene Expression ◽  
Response Regulator ◽  
Regulation Of Gene Expression ◽  
Leptospira Interrogans ◽  
Mrna Levels ◽  
Genetic Circuits ◽  
Positive Regulation ◽  
Content Type ◽  
Novel Approach ◽  
In The Wild

ABSTRACTLeptospirosis is a potentially deadly zoonotic disease that afflicts humans and animals.Leptospira interrogans, the predominant agent of leptospirosis, encounters diverse conditions as it proceeds through its life cycle, which includes stages inside and outside the host. Unfortunately, the number of genetic tools available for examining the regulation of gene expression inL. interrogansis limited. Consequently, little is known about the genetic circuits that control gene expression inLeptospira. To better understand the regulation of leptospiral gene expression, theL. interrogans kdplocus, encoding homologs of the P-type ATPase KdpABC potassium transporter with their KdpD sensors and KdpE response regulators, was selected for analysis. We showed that akdpEmutation inL. interrogansprevented the increase inkdpABCmRNA levels observed in the wild-typeL. interrogansstrain when external potassium levels were low. To confirm that KdpE was a positive regulator ofkdpABCtranscription, we developed a novel approach for constructing chromosomal genetic fusions to the endogenousbgaL(β-galactosidase) gene of the nonpathogenLeptospira biflexa. We demonstrated positive regulation of akdpA′-bgaLfusion inL. biflexaby theL. interrogansKdpE response regulator. A controllipL32′-bgaLfusion was not regulated by KdpE. These results demonstrate the utility of genetic fusions to thebgaLgene ofL. biflexafor examining leptospiral gene regulation.

Polyploidization-induced genome variation in triticale

Genome ◽  
2004 ◽  
Vol 47 (5) ◽  
pp. 839-848 ◽  
Author(s):  
Xue-Feng Ma ◽  
Peng Fang ◽  
J Perry Gustafson
Keyword(s):  
Genome Evolution ◽  
Cytosine Methylation ◽  
Genomic Sequence ◽  
Repetitive Sequences ◽  
Genomic Sequences ◽  
Addition Lines ◽  
Ploidy Levels ◽  
Coding Sequences ◽  
Genome Variation ◽  
Aflp Band

Polyploidization-induced genome variation in triticale (× Triticosecale Wittmack) was investigated using both AFLP and RFLP analyses. The AFLP analyses were implemented with both EcoRI–MseI (E–M) and PstI–MseI (P–M) primer combinations, which, because of their relative differences in sensitivity to cytosine methylation, primarily amplify repetitive and low-copy sequences, respectively. The results showed that the genomic sequences in triticale involved a great degree of variation including both repetitive and low-copy sequences. The frequency of losing parental bands was much higher than the frequency of gaining novel bands, suggesting that sequence elimination might be a major force causing genome variation in triticale. In all cases, variation in E–M primer-amplified parental bands was more frequent in triticale than that using P–M primers, suggesting that repetitive sequences were more involved in variation than low-copy sequences. The data also showed that the wheat (Triticum spp.) genomes were relatively highly conserved in triticales, especially in octoploid triticales, whereas the rye (Secale cereale L.) genome consistently demonstrated a very high level of genomic sequence variation (68%–72%) regardless of the triticale ploidy levels or primers used. In addition, when a parental AFLP band was present in both wheat and rye, the tendency of the AFLP band to be present in triticale was much higher than when it was present in only one of the progenitors. Furthermore, the cDNA-probed RFLP analyses showed that over 97% of the wheat coding sequences were maintained in triticale, whereas only about 61.6% of the rye coding sequences were maintained, suggesting that the rye genome variation in triticale also involved a high degree of rye coding sequence changes. The data also suggested that concerted evolution might occur in the genomic sequences of triticale. In addition, the observed genome variation in wheat–rye addition lines was similar to that in triticale, suggesting that wheat–rye addition lines can be used to thoroughly study the genome evolution of polyploid triticale.Key words: wheat, rye, polyploid, genome evolution, sequence elimination.

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