Eggs, embryos and the evolution of imprinting: insights from the platypus genome

2009 ◽  
Vol 21 (8) ◽  
pp. 935 ◽  
Author(s):  
Marilyn B. Renfree ◽  
Anthony T. Papenfuss ◽  
Geoff Shaw ◽  
Andrew J. Pask
Keyword(s):  
Genomic Imprinting ◽  
Large Scale ◽  
Strong Support ◽  
Gene Clusters ◽  
Host Defence ◽  
Long Terminal Repeats ◽  
Repeat Elements ◽  
Platypus Genome ◽  
Dna Elements ◽  
Genome Analyses

Genomic imprinting is widespread in eutherian and marsupial mammals. Although there have been many hypotheses to explain why genomic imprinting evolved in mammals, few have examined how it arose. The host defence hypothesis suggests that imprinting evolved from existing mechanisms within the cell that act to silence foreign DNA elements that insert into the genome. However, the changes to the mammalian genome that accompanied the evolution of imprinting have been hard to define due to the absence of large-scale genomic resources from all extant classes. The recent release of the platypus genome sequence has provided the first opportunity to make comparisons between prototherian (monotreme, which show no signs of imprinting) and therian (marsupial and eutherian, which have imprinting) mammals. We compared the distribution of repeat elements known to attract epigenetic silencing across the genome from monotremes and therian mammals, particularly focusing on the orthologous imprinted regions. Our analyses show that the platypus has significantly fewer repeats of certain classes in the regions of the genome that have become imprinted in therian mammals. The accumulation of repeats, especially long-terminal repeats and DNA elements, in therian imprinted genes and gene clusters therefore appears to be coincident with, and may have been a potential driving force in, the development of mammalian genomic imprinting. Comparative platypus genome analyses of orthologous imprinted regions have provided strong support for the host defence hypothesis to explain the origin of imprinting.

scholarly journals Large-Scale, High-Throughput Validation of Short Hairpin RNA Sequences for RNA Interference

2006 ◽  
Vol 11 (3) ◽  
pp. 236-246 ◽  
Author(s):  
Laurence H. Lamarcq ◽  
Bradley J. Scherer ◽  
Michael L. Phelan ◽  
Nikolai N. Kalnine ◽  
Yen H. Nguyen ◽  
...  
Keyword(s):  
High Throughput ◽  
Large Scale ◽  
Strong Support ◽  
Gc Content ◽  
Rapid Identification ◽  
Hairpin Rna ◽  
Rna Sequences ◽  
Short Hairpin ◽  
Short Hairpin Rnas ◽  
Interfering Rna

A method for high-throughput cloning and analysis of short hairpin RNAs (shRNAs) is described. Using this approach, 464 shRNAs against 116 different genes were screened for knockdown efficacy, enabling rapid identification of effective shRNAs against 74 genes. Statistical analysis of the effects of various criteria on the activity of the shRNAs confirmed that some of the rules thought to govern small interfering RNA (siRNA) activity also apply to shRNAs. These include moderate GC content, absence of internal hairpins, and asymmetric thermal stability. However, the authors did not find strong support for positionspecific rules. In addition, analysis of the data suggests that not all genes are equally susceptible to RNAinterference (RNAi).

scholarly journals Current advances of epigenetics in periodontology from ENCODE project: a review and future perspectives

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Young-Dan Cho ◽  
Woo-Jin Kim ◽  
Hyun-Mo Ryoo ◽  
Hong-Gee Kim ◽  
Kyoung-Hwa Kim ◽  
...  
Keyword(s):  
Large Scale ◽  
Periodontal Diseases ◽  
Research Trends ◽  
Main Body ◽  
Research Projects ◽  
Encode Project ◽  
Dna Elements ◽  
Crucial Information ◽  
Future Direction ◽  
Systemic Health

Abstract Background The Encyclopedia of DNA Elements (ENCODE) project has advanced our knowledge of the functional elements in the genome and epigenome. The aim of this article was to provide the comprehension about current research trends from ENCODE project and establish the link between epigenetics and periodontal diseases based on epigenome studies and seek the future direction. Main body Global epigenome research projects have emphasized the importance of epigenetic research for understanding human health and disease, and current international consortia show an improved interest in the importance of oral health with systemic health. The epigenetic studies in dental field have been mainly conducted in periodontology and have focused on DNA methylation analysis. Advances in sequencing technology have broadened the target for epigenetic studies from specific genes to genome-wide analyses. Conclusions In line with global research trends, further extended and advanced epigenetic studies would provide crucial information for the realization of comprehensive dental medicine and expand the scope of ongoing large-scale research projects.

scholarly journals Role of Methylation in the Induced and Spontaneous Expression of the Avian Endogenous Virusev-1: DNA Structure and Gene Products

1982 ◽  
Vol 2 (6) ◽  
pp. 638-652 ◽  
Author(s):  
Kathleen F. Conklin ◽  
John M. Coffin ◽  
Harriet L. Robinson ◽  
Mark Groudine ◽  
Robert Eisenman
Keyword(s):  
Dna Methylation ◽  
Strong Support ◽  
Reverse Transcriptase Activity ◽  
Structural Defects ◽  
Long Terminal Repeats ◽  
Control Of Gene Expression ◽  
Rna Molecules ◽  
Hypersensitive Sites ◽  
High Level

The endogenous avian provirusev-1 is widespread in white leghorn chickens. Although it has no major structural defects,ev-1 has not been associated with any phenotype and is ordinarily expressed at a very low level. In this report, we describe a chicken embryo (Number 1836) cell culture containing bothev-1 andev-6 which spontaneously expressed theev-1 provirus. This culture released a high level of noninfectious virions containing a full complement of virion structural (gag) proteins but devoid of reverse transcriptase activity or antigen. These virions contained 70S RNA closely related to the genome of Rous-associated virus type 0, but identifiable as theev-1 genome by oligonucleotide mapping. A fraction of the RNA molecules in the 70S complex were unusual in that they were polyadenylated 100 to 200 nucleotides downstream of the usual polyadenylation site. Eight sibling embryo cultures did not share this unusual phenotype with 1836, indicating that it was not inherited. However, an identical phenotype was inducible in the sibling cultures by treatment with 5-azacytidine, an inhibitor of DNA methylation, and the induced expression was stable for more than 10 generations. Analysis of chromatin structure and DNA methylation of theev-1 provirus in 1836 cells revealed the presence (in a fraction of the proviruses) of both DNase I hypersensitive sites in the long terminal repeats and ingagand a pattern of cleavage sites for methyl-sensitive restriction endonuclease not found in a nonexpressing sibling. These results lend strong support to the role of DNA methylation in the control of gene expression. Additionally, they explain the lack of phenotype associated withev-1 as due to a combination of its low expression and defectiveness inpolandenv.

scholarly journals Dynamics of Genome Architecture in Rhizobium sp. Strain NGR234

2002 ◽  
Vol 184 (1) ◽  
pp. 171-176 ◽  
Author(s):  
Patrick Mavingui ◽  
Margarita Flores ◽  
Xianwu Guo ◽  
Guillermo Dávila ◽  
Xavier Perret ◽  
...  
Keyword(s):  
Large Scale ◽  
Insertion Sequence ◽  
Biological Significance ◽  
Genome Architecture ◽  
Bacterial Genomes ◽  
Symbiotic Plasmid ◽  
Sequence Elements ◽  
Dynamic Structures ◽  
Genome Analyses ◽  
Insertion Sequence Elements

ABSTRACT Bacterial genomes are usually partitioned in several replicons, which are dynamic structures prone to mutation and genomic rearrangements, thus contributing to genome evolution. Nevertheless, much remains to be learned about the origins and dynamics of the formation of bacterial alternative genomic states and their possible biological consequences. To address these issues, we have studied the dynamics of the genome architecture in Rhizobium sp. strain NGR234 and analyzed its biological significance. NGR234 genome consists of three replicons: the symbiotic plasmid pNGR234a (536,165 bp), the megaplasmid pNGR234b (>2,000 kb), and the chromosome (>3,700 kb). Here we report that genome analyses of cell siblings showed the occurrence of large-scale DNA rearrangements consisting of cointegrations and excisions between the three replicons. As a result, four new genomic architectures have emerged. Three consisted of the cointegrates between two replicons: chromosome-pNGR234a, chromosome-pNGR234b, and pNGR234a-pNGR234b. The other consisted of a cointegrate of the three replicons (chromosome-pNGR234a-pNGR234b). Cointegration and excision of pNGR234a with either the chromosome or pNGR234b were studied and found to proceed via a Campbell-type mechanism, mediated by insertion sequence elements. We provide evidence showing that changes in the genome architecture did not alter the growth and symbiotic proficiency of Rhizobium derivatives.

scholarly journals CAF and CAMM analyses on the first 10 years of national Kanta services in Finland

2020 ◽  
Vol 12 (4) ◽  
Author(s):  
Vesa Jormanainen ◽  
Jarmo Reponen
Keyword(s):  
Health Information ◽  
Large Scale ◽  
National Level ◽  
Health Information System ◽  
Strong Support ◽  
Evaluation Framework ◽  
Macro Level ◽  
State Budget ◽  
Study Results ◽  
Clinical Adoption

We report the large-scale deployment, implementation and adoption of the nationwide centralized integrated and shared Kanta health information services by using the Clinical Adoption Framework (CAF). The meso and macro level dimensions of the CAF were incorporated early into our e-health evaluation framework to assess Health Information System (HIS) implementation at the national level. We found strong support for the CAF macro level model concepts in Finland. Typically, development programs were followed by government policy commitments, appropriate legislation and state budget funding before the CAF meso level implementation activities. Our quantitative data point to the fact that implementing large-scale health information technology (HIT) systems in practice is a rather long process. For HIT systems success in particular citizens’ and professionals’ acceptance are essential. When implementation of the national health information systems was evaluated against Clinical Adoption Meta-Model (CAMM), the results show that Finland has already passed many milestones in CAMM archetypes. According to our study results, Finland seems to be a good laboratory entity to study practical execution of HIT systems, CAF and CAMM theoretical constructs can be used for national level HIS implementation evaluation.

scholarly journals Ragnarok

1996 ◽  
Vol 25 (509) ◽  
Author(s):  
Henrik Bærbak Christensen
Keyword(s):  
Project Management ◽  
Software Development ◽  
Large Scale ◽  
Strong Support ◽  
Current State ◽  
Industrial Strength ◽  
Software Development Environments

<p>This report describes the current state of my research in software development environments. I argue in favour of strong support for <em>project management, comprehension and navigation,</em> and <em>collaboration</em> primarily based on experiences from developing large-scale industrial-strength applications.</p><p>An underlying model of such an environment, named ``Ragnarok´´, is outlined. A design and first prototype of important parts of Ragnarok is described as well as some results from initial experiments.</p>

scholarly journals Genetic structure, function and evolution of capsule biosynthesis loci in Vibrio parahaemolyticus

2020 ◽  
Author(s):  
Shengzhe Bian ◽  
Zeng Wenhong ◽  
Qiwen Li ◽  
Yinghui Li ◽  
Nai-Kei Wong ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Vibrio Parahaemolyticus ◽  
Large Scale ◽  
Gene Clusters ◽  
New Right ◽  
Important Food ◽  
Nonsense Mutations ◽  
Food Borne ◽  
Right Border ◽  
First Time

AbstractCapsule-forming extracellular polysaccharides are crucial to bacterial host colonization, invasion, immune evasion and ultimately pathogenicity. Due to warming ocean waters and human encroachment of coastal ecosystems, Vibrio parahaemolyticus has emerged as a globally important food-borne enteropathogen implicated in acute gastroenteritis, wound infections, and septic shock. Conventionally, the antigenic properties of lipopolysaccharide (LPS, O antigen) and capsular polysaccharide (CPS, K antigen) have provided a basis for serotyping V. parahaemolyticus, while disclosure of genetic elements encoding 13 O-serogroups have allowed molecular serotyping methods to be developed. However, the genetic structure of CPS loci for 71 K-serogroups has remained unidentified, limiting progress in understanding its roles in V. parahaemolyticus pathophysiology. In this study, we identified and characterized the genetic structure and their evolutionary relationship of CPS loci of 40 K-serogroups through whole genome sequencing of 443 V. parahaemolyticus strains. We found a distinct pattern of CPS gene cluster across different K-serogroups, and expanded its new right-border by identifying glpX as a key gene conserved across all serotypes. A total of 217 genes involved in CPS biosynthesis were annotated. Functional contents and genetic structure of the 40 K-serogroups were analyzed. Based on inferences from species trees and gene trees, we proposed an evolution model of the CPS gene clusters of 40 K-serogroups. Horizontal gene transfer by recombination from other Vibrio species, gene duplication and nonsense mutations are likely to play instrumental roles in the evolution of CPS in V. parahaemolyticus. It is the first time, to the best of our knowledge, that a large-scale of CPS gene clusters of different K-serogroups in V. parahaemolyticus have been identified and characterized in evolutionary contexts. This work should help advance understanding on the variation of CPS in V. parahaemolyticus, and provide a framework for developing diagnostically relevant serotyping methods.Author summaryDue to warming ocean waters and human encroachment of coastal ecosystems, Vibrio parahaemolyticus has emerged as a globally important food-borne enteropathogen. However, the genetic structure of CPS loci for 71 K-serogroups V. parahaemolyticus have remained unidentified, limiting progress in understanding its roles in V. parahaemolyticus pathophysiology. In this study, we identified and characterized the genetic structure of CPS loci of 40 K-serogroups through whole genome sequencing of 443 V. parahaemolyticus strains. We expanded and identified its new right-border by identifying glpX as a key gene conserved across all serotypes. We proposed an evolution model of the CPS gene clusters of 40 K-serogroups. We also found horizontal gene transfer by recombination from other Vibrio species, gene duplication and nonsense mutations are likely to play instrumental roles in the evolution of CPS in V. parahaemolyticus. It is the first time, to the best of our knowledge, that a large-scale of CPS loci of different K-serogroups in V. parahaemolyticus have been identified and characterized in evolutionary contexts. This work should help advance understanding on the variation of CPS in V. parahaemolyticus, and provide a framework for developing diagnostically relevant serotyping methods.

scholarly journals Refactoring the formicamycin biosynthetic gene cluster to make high-level producing strains and new molecules

2020 ◽  
Author(s):  
Rebecca Devine ◽  
Hannah McDonald ◽  
Zhiwei Qin ◽  
Corinne Arnold ◽  
Katie Noble ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Large Scale ◽  
Liquid Culture ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Biosynthetic Gene ◽  
Biosynthetic Genes

AbstractThe formicamycins are promising antibiotics with potent activity against Gram-positive pathogens including VRE and MRSA and display a high barrier to selection of resistant isolates. They were first identified in Streptomyces formicae KY5, which produces the formicamycins at low levels on solid agar but not in liquid culture, thus hindering further investigation of these promising antibacterial compounds. We hypothesised that by understanding the organisation and regulation of the for biosynthetic gene cluster, we could rationally refactor the cluster to increase production levels. Here we report that the for biosynthetic gene cluster consists of 24 genes expressed on nine transcripts. Seven of these transcripts, including those containing all the major biosynthetic genes, are repressed by the MarR-regulator ForJ which also controls the expression of the ForGF two-component system that initiates biosynthesis. A third cluster-situated regulator, ForZ, autoregulates and controls production of the putative MFS transporter ForAA. Consistent with these findings, deletion of forJ increased formicamycin biosynthesis 5-fold, while over-expression of forGF in the ΔforJ background increased production 10-fold compared to the wild-type. De-repression by deleting forJ also switched on biosynthesis in liquid-culture and induced the production of two novel formicamycin congeners. By combining mutations in regulatory and biosynthetic genes, six new biosynthetic precursors with antibacterial activity were also isolated. This work demonstrates the power of synthetic biology for the rational redesign of antibiotic biosynthetic gene clusters both to engineer strains suitable for fermentation in large scale bioreactors and to generate new molecules.ImportanceAntimicrobial resistance is a growing threat as existing antibiotics become increasingly ineffective against drug resistant pathogens. Here we determine the transcriptional organisation and regulation of the gene cluster encoding biosynthesis of the formicamycins, promising new antibiotics with activity against drug resistant bacteria. By exploiting this knowledge, we construct stable mutant strains which over-produce these molecules in both liquid and solid culture whilst also making some new compound variants. This will facilitate large scale purification of these molecules for further study including in vivo experiments and the elucidation of their mechanism of action. Our work demonstrates that understanding the regulation of natural product biosynthetic pathways can enable rational improvement of the producing strains.

scholarly journals DISRUPTION OF CPG ISLAND-MEDIATED CHROMATIN ARCHITECTURE AND TRANSCRIPTIONAL HOMEOSTASIS DURING AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S208-S208
Author(s):  
Samuel Beck ◽  
Junyeong Lee
Keyword(s):  
Large Scale ◽  
Cpg Island ◽  
Expression Patterns ◽  
Cpg Islands ◽  
Nuclear Lamina ◽  
The Body ◽  
Chromatin Architecture ◽  
Age Related ◽  
Dna Elements ◽  
Computational Analyses

Abstract Aging causes the global disorganization of nuclear chromatin architecture. In a normal young nucleus, silent heterochromatin is associated with the nuclear lamina layer underlying nuclear envelope, thus spatially separated from euchromatin at the nuclear center. Notably, aging causes the disruption of nuclear lamina and the decondensation of associated heterochromatin. However, it is not clearly understood how these changes of chromatin architectures contribute to age-related diseases. Through large-scale computational analyses, we present that CpG islands (CGIs) give important clues to answering this question. CGIs are DNA elements with high Cytosine-phosphate-Guanine dinucleotide frequencies. In human, about 60% of total genes contain CGIs at their promoters (CGI+ genes) and are broadly expressed throughout the body. The other 40% of genes that do not have CGIs (CGI- genes) exhibit tissue-restricted expression patterns. Our results demonstrate that, in normal young nuclei, only CGI- genes can reside within lamina-associated heterochromatin when transcriptionally inactive, while CGI+ genes associate with nuclear central euchromatin even when they are repressed. In parallel, we show that age-associated heterochromatin decondensation can specifically de-repress tissue-specific CGI- genes leading to their uncontrolled expressions. Our results further demonstrate that global misregulation of CGI- genes increases the noise in gene transcription that, in turn, causes the loss of cellular identities during aging. Taken together, our study establishes critical implication of CGI-mediated chromatin architecture in age-associated degenerative changes and loss of tissue homeostasis.

scholarly journals BioPartsBuilder: a synthetic biology tool for combinatorial assembly of biological parts

2015 ◽  
Vol 32 (6) ◽  
pp. 937-939 ◽  
Author(s):  
Kun Yang ◽  
Giovanni Stracquadanio ◽  
Jingchuan Luo ◽  
Jef D. Boeke ◽  
Joel S. Bader
Keyword(s):  
Large Scale ◽  
Supplementary Information ◽  
Market Place ◽  
Design Standards ◽  
Reusable Components ◽  
Assembly Design ◽  
Amazon Web Services ◽  
Dna Elements ◽  
Combinatorial Assembly ◽  
The Cost

Abstract Summary: Combinatorial assembly of DNA elements is an efficient method for building large-scale synthetic pathways from standardized, reusable components. These methods are particularly useful because they enable assembly of multiple DNA fragments in one reaction, at the cost of requiring that each fragment satisfies design constraints. We developed BioPartsBuilder as a biologist-friendly web tool to design biological parts that are compatible with DNA combinatorial assembly methods, such as Golden Gate and related methods. It retrieves biological sequences, enforces compliance with assembly design standards and provides a fabrication plan for each fragment. Availability and implementation: BioPartsBuilder is accessible at http://public.biopartsbuilder.org and an Amazon Web Services image is available from the AWS Market Place (AMI ID: ami-508acf38). Source code is released under the MIT license, and available for download at https://github.com/baderzone/biopartsbuilder. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

Sign in / Sign up

Export Citation Format

Share Document