The Role of Chromatid Interference in Determining Meiotic Crossover Patterns

Plants, like all sexually reproducing organisms, create genetic variability by reshuffling parental alleles during meiosis. Patterns of genetic variation in the resulting gametes are determined by the independent assortment of chromosomes in meiosis I and by the number and positioning of crossover (CO) events during meiotic recombination. On the chromosome level, spatial distribution of CO events is biased by multiple regulatory mechanisms, such as CO assurance, interference and homeostasis. However, little is known about how multiple COs are distributed among the four chromatids of a bivalent. Chromatid interference (CI) has been proposed as a regulatory mechanism that biases distribution of multiple COs toward specific chromatid partners, however, its existence has not been well-studied and its putative mechanistic basis remains undescribed. Here, we introduce a novel method to quantitatively express CI, and take advantage of available tetrad-based genotyping data from Arabidopsis and maize male meiosis to quantify CI effects on a genome-wide and chromosomal scale. Overall, our analyses reveal random involvement of sister chromatids in double CO events across paired chromosomes, indicating an absence of CI. However, on a genome-wide level, CI was found to vary with physical distance between COs, albeit with different effects in Arabidopsis and maize. While effects of CI are minor in Arabidopsis and maize, the novel methodology introduced here enables quantitative interpretation of CI both on a local and genome-wide scale, and thus provides a key tool to study CI with relevance for both plant genetics and crop breeding.

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Requirement of splicing factor hnRNP A2B1 of hnRNPs for tumorigenesis of melanoma stem cells

10.21203/rs.3.rs-92870/v1 ◽

2020 ◽

Author(s):

Mengqi Chu ◽

Haitao Wan ◽

Xiaobo Zhang

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Therapy ◽

Cycle Arrest ◽

Genome Wide ◽

A Genome ◽

Rna Immunoprecipitation ◽

Wide Scale

Abstract Background: Cancer stem cells play essential roles in tumorigenesis, thus being the important targets for tumor therapy. The hnRNP family proteins, the important splicing factors, are found to be associated with tumor progression. However, the influence of hnRNPs on cancer stem cells has not been extensively explored.Methods: Quantitative real-time PCR and Western blot were used to examine the gene expression level. RNA immunoprecipitation assay and RNA sequencing were conducted to identify the RNAs interacted with hnRNP A2B1 on a genome-wide scale. The in vivo assays were performed in nude mice.Results: In this study, the results showed that hnRNP A2B1 of 19 hnRNPs was significantly upregulated in melanoma stem cells compared with non-stem cells, suggesting the important role of hnRNP A2B1 in cancer stem cells. The hnRNP A2B1 silencing triggered the cell cycle arrest in G2 phase, leading to apoptosis of melanoma stem cells. The results revealed that hnRNP A2B1 could bind to the precursor mRNAs of pro-apoptosis genes (DAPK1, SYT7 and RNF128) and anti-apoptosis genes (EIF3H, TPPP3 and DOCK2) to regulate the splicing of these 6 genes, thus promoting the expressions of anti-apoptosis genes and suppressing the expressions of pro-apoptosis genes. The in vivo data indicated that hnRNP A2B1 was required for tumorigenesis of melanoma stem cells in vivo by affecting the splicing of TPPP3, DOCK2, EIF3H, RNF128, DAPK1 and SYT7, thus suppressing apoptosis of melanoma stem cells.Conclusions: HnRNP A2B1 was required for tumorigenesis of melanoma stem cells. Therefore our findings presented novel molecular insights into the roles of hnRNPs in cancer stem cells.

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Pharmacoepigenetics and Pharmacoepigenomics: An Overview

Current Drug Discovery Technologies ◽

10.2174/1570163815666180419154633 ◽

2019 ◽

Vol 16 (4) ◽

pp. 392-399 ◽

Cited By ~ 2

Author(s):

Jacob Peedicayil

Keyword(s):

Drug Resistance ◽

Clinical Practice ◽

Epigenetic Therapy ◽

Drug Reactions ◽

Epigenetic Biomarkers ◽

Genome Wide ◽

A Genome ◽

Wide Scale ◽

Made In

Background: The rapid and major advances being made in epigenetics are impacting pharmacology, giving rise to new sub-disciplines in pharmacology, pharmacoepigenetics, the study of the epigenetic basis of variation in response to drugs; and pharmacoepigenomics, the application of pharmacoepigenetics on a genome-wide scale. Methods: This article highlights the following aspects of pharmacoepigenetics and pharmacoepigenomics: epigenetic therapy, the role of epigenetics in pharmacokinetics, the relevance of epigenetics to adverse drug reactions, personalized medicine, drug addiction, and drug resistance, and the use of epigenetic biomarkers in drug therapy. Results: Epigenetics is having an increasing impact on several areas of pharmacology. Conclusion: Pharmacoepigenetics and pharmacoepigenomics are new sub-disciplines in pharmacology and are likely to have an increasing impact on the use of drugs in clinical practice.

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The role of proteomics in investigating psychiatric disorders

The British Journal of Psychiatry ◽

10.1192/bjp.187.1.4 ◽

2005 ◽

Vol 187 (1) ◽

pp. 4-6 ◽

Cited By ~ 8

Author(s):

K. Pennington ◽

D. Cotter ◽

M. J. Dunn

Keyword(s):

Protein Expression ◽

Psychiatric Disorders ◽

Psychiatric Research ◽

Psychiatric Disease ◽

Genome Wide ◽

A Genome ◽

Wide Scale ◽

New Treatments ◽

And Function

SummaryProteomics is the study of protein expression and function on a genome-wide scale and its application in psychiatric research is relatively new. As protein expression is the mediator of genetic vulnerabilities, it is critical that this area is explored further to increase our understanding of psychiatric disease and reveal potential new treatments.

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A Genome-Wide Analysis of Pathogenesis-Related Protein-1 (PR-1) Genes from Piper nigrum Reveals Its Critical Role during Phytophthora capsici Infection

Genes ◽

10.3390/genes12071007 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1007

Author(s):

Divya Kattupalli ◽

Asha Sreenivasan ◽

Eppurathu Vasudevan Soniya

Keyword(s):

Phytophthora Capsici ◽

Regulatory Elements ◽

Piper Nigrum ◽

Binding Motif ◽

Altered Expression ◽

Genome Wide ◽

A Genome ◽

Pathogenesis Related Protein ◽

Pathogenesis Related

Black pepper (Piper nigrum L.) is a prominent spice that is an indispensable ingredient in cuisine and traditional medicine. Phytophthora capsici, the causative agent of footrot disease, causes a drastic constraint in P. nigrum cultivation and productivity. To counterattack various biotic and abiotic stresses, plants employ a broad array of mechanisms that includes the accumulation of pathogenesis-related (PR) proteins. Through a genome-wide survey, eleven PR-1 genes that belong to a CAP superfamily protein with a caveolin-binding motif (CBM) and a CAP-derived peptide (CAPE) were identified from P. nigrum. Despite the critical functional domains, PnPR-1 homologs differ in their signal peptide motifs and core amino acid composition in the functional protein domains. The conserved motifs of PnPR-1 proteins were identified using MEME. Most of the PnPR-1 proteins were basic in nature. Secondary and 3D structure analyses of the PnPR-1 proteins were also predicted, which may be linked to a functional role in P. nigrum. The GO and KEGG functional annotations predicted their function in the defense responses of plant-pathogen interactions. Furthermore, a transcriptome-assisted FPKM analysis revealed PnPR-1 genes mapped to the P. nigrum-P. capsici interaction pathway. An altered expression pattern was detected for PnPR-1 transcripts among which a significant upregulation was noted for basic PnPR-1 genes such as CL10113.C1 and Unigene17664. The drastic variation in the transcript levels of CL10113.C1 was further validated through qRT-PCR and it showed a significant upregulation in infected leaf samples compared with the control. A subsequent analysis revealed the structural details, phylogenetic relationships, conserved sequence motifs and critical cis-regulatory elements of PnPR-1 genes. This is the first genome-wide study that identified the role of PR-1 genes during P. nigrum-P. capsici interactions. The detailed in silico experimental analysis revealed the vital role of PnPR-1 genes in regulating the first layer of defense towards a P. capsici infection in Panniyur-1 plants.

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F-Box Genes in the Wheat Genome and Expression Profiling in Wheat at Different Developmental Stages

Genes ◽

10.3390/genes11101154 ◽

2020 ◽

Vol 11 (10) ◽

pp. 1154

Author(s):

Min Jeong Hong ◽

Jin-Baek Kim ◽

Yong Weon Seo ◽

Dae Yeon Kim

Keyword(s):

Developmental Stages ◽

Brachypodium Distachyon ◽

Triticum Aestivum L ◽

Wheat Genome ◽

Post Translational Modification ◽

Genome Wide ◽

A Genome ◽

High Sequence Homology ◽

Wide Scale

Genes of the F-box family play specific roles in protein degradation by post-translational modification in several biological processes, including flowering, the regulation of circadian rhythms, photomorphogenesis, seed development, leaf senescence, and hormone signaling. F-box genes have not been previously investigated on a genome-wide scale; however, the establishment of the wheat (Triticum aestivum L.) reference genome sequence enabled a genome-based examination of the F-box genes to be conducted in the present study. In total, 1796 F-box genes were detected in the wheat genome and classified into various subgroups based on their functional C-terminal domain. The F-box genes were distributed among 21 chromosomes and most showed high sequence homology with F-box genes located on the homoeologous chromosomes because of allohexaploidy in the wheat genome. Additionally, a synteny analysis of wheat F-box genes was conducted in rice and Brachypodium distachyon. Transcriptome analysis during various wheat developmental stages and expression analysis by quantitative real-time PCR revealed that some F-box genes were specifically expressed in the vegetative and/or seed developmental stages. A genome-based examination and classification of F-box genes provide an opportunity to elucidate the biological functions of F-box genes in wheat.

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Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network

Nucleic Acids Research ◽

10.1093/nar/gku576 ◽

2014 ◽

Vol 42 (15) ◽

pp. 9838-9853 ◽

Cited By ~ 6

Author(s):

Saeed Kaboli ◽

Takuya Yamakawa ◽

Keisuke Sunada ◽

Tao Takagaki ◽

Yu Sasano ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Genetic Interaction ◽

Interaction Network ◽

Essential Genes ◽

Genetic Interactions ◽

Lethal Gene ◽

Synthetic Lethal ◽

Genome Wide ◽

A Genome ◽

Wide Scale

Abstract Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. Here, we attempted to delete these regions by PCR-mediated chromosomal deletion technology (PCD), which enables chromosomal segments to be deleted by a one-step transformation. Thirty-three of the 110 regions could be deleted, but the remaining 77 regions could not. To determine whether the 77 undeletable regions are essential, we successfully converted 67 of them to mini-chromosomes marked with URA3 using PCR-mediated chromosome splitting technology and conducted a mitotic loss assay of the mini-chromosomes. Fifty-six of the 67 regions were found to be essential for cell growth, and 49 of these carried co-lethal gene pair(s) that were not previously been detected by synthetic genetic array analysis. This result implies that regions harboring only non-essential genes contain unidentified synthetic lethal combinations at an unexpectedly high frequency, revealing a novel landscape of genetic interactions in the S. cerevisiae genome. Furthermore, this study indicates that segmental deletion might be exploited for not only revealing genome function but also breeding stress-tolerant strains.

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Comprehensive Genomic Discovery of Non-Coding Transcriptional Enhancers in the African Malaria Vector Anopheles coluzzii

Frontiers in Genetics ◽

10.3389/fgene.2021.785934 ◽

2022 ◽

Vol 12 ◽

Author(s):

Inge Holm ◽

Luisa Nardini ◽

Adrien Pain ◽

Emmanuel Bischoff ◽

Cameron E. Anderson ◽

...

Keyword(s):

Malaria Vector ◽

Regulatory Elements ◽

Specific Cell ◽

Insect Vector ◽

Anopheles Coluzzii ◽

Gene Promoters ◽

Transcriptional Enhancers ◽

Genome Wide ◽

A Genome

Almost all regulation of gene expression in eukaryotic genomes is mediated by the action of distant non-coding transcriptional enhancers upon proximal gene promoters. Enhancer locations cannot be accurately predicted bioinformatically because of the absence of a defined sequence code, and thus functional assays are required for their direct detection. Here we used a massively parallel reporter assay, Self-Transcribing Active Regulatory Region sequencing (STARR-seq), to generate the first comprehensive genome-wide map of enhancers in Anopheles coluzzii, a major African malaria vector in the Gambiae species complex. The screen was carried out by transfecting reporter libraries created from the genomic DNA of 60 wild A. coluzzii from Burkina Faso into A. coluzzii 4a3A cells, in order to functionally query enhancer activity of the natural population within the homologous cellular context. We report a catalog of 3,288 active genomic enhancers that were significant across three biological replicates, 74% of them located in intergenic and intronic regions. The STARR-seq enhancer screen is chromatin-free and thus detects inherent activity of a comprehensive catalog of enhancers that may be restricted in vivo to specific cell types or developmental stages. Testing of a validation panel of enhancer candidates using manual luciferase assays confirmed enhancer function in 26 of 28 (93%) of the candidates over a wide dynamic range of activity from two to at least 16-fold activity above baseline. The enhancers occupy only 0.7% of the genome, and display distinct composition features. The enhancer compartment is significantly enriched for 15 transcription factor binding site signatures, and displays divergence for specific dinucleotide repeats, as compared to matched non-enhancer genomic controls. The genome-wide catalog of A. coluzzii enhancers is publicly available in a simple searchable graphic format. This enhancer catalogue will be valuable in linking genetic and phenotypic variation, in identifying regulatory elements that could be employed in vector manipulation, and in better targeting of chromosome editing to minimize extraneous regulation influences on the introduced sequences.Importance: Understanding the role of the non-coding regulatory genome in complex disease phenotypes is essential, but even in well-characterized model organisms, identification of regulatory regions within the vast non-coding genome remains a challenge. We used a large-scale assay to generate a genome wide map of transcriptional enhancers. Such a catalogue for the important malaria vector, Anopheles coluzzii, will be an important research tool as the role of non-coding regulatory variation in differential susceptibility to malaria infection is explored and as a public resource for research on this important insect vector of disease.

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The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission

10.1101/2020.08.25.266775 ◽

2020 ◽

Cited By ~ 8

Author(s):

Yunkai Zhu ◽

Fei Feng ◽

Gaowei Hu ◽

Yuyan Wang ◽

Yin Yu ◽

...

Keyword(s):

Critical Role ◽

Surface Expression ◽

Spike Protein ◽

Hamster Model ◽

Entry Pathway ◽

Genome Wide ◽

A Genome ◽

Model Animal ◽

Public Health Challenges

SUMMARYThe global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission.

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Machine-learning annotation of human splicing branchpoints

10.1101/094003 ◽

2016 ◽

Cited By ~ 3

Author(s):

Bethany Signal ◽

Brian S Gloss ◽

Marcel E Dinger ◽

Timothy R Mercer

Keyword(s):

Machine Learning ◽

Learning Algorithm ◽

Gene Splicing ◽

Genetic Encoding ◽

Genome Wide ◽

Common Genetic Variants ◽

A Genome ◽

Wide Scale ◽

The Impact ◽

Splicing Patterns

ABSTRACTBackgroundThe branchpoint element is required for the first lariat-forming reaction in splicing. However due to difficulty in experimentally mapping at a genome-wide scale, current catalogues are incomplete.ResultsWe have developed a machine-learning algorithm trained with empirical human branchpoint annotations to identify branchpoint elements from primary genome sequence alone. Using this approach, we can accurately locate branchpoints elements in 85% of introns in current gene annotations. Consistent with branchpoints as basal genetic elements, we find our annotation is unbiased towards gene type and expression levels. A major fraction of introns was found to encode multiple branchpoints raising the prospect that mutational redundancy is encoded in key genes. We also confirmed all deleterious branchpoint mutations annotated in clinical variant databases, and further identified thousands of clinical and common genetic variants with similar predicted effects.ConclusionsWe propose the broad annotation of branchpoints constitutes a valuable resource for further investigations into the genetic encoding of splicing patterns, and interpreting the impact of common- and disease-causing human genetic variation on gene splicing.

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Emerging Technologies for Genome-Wide Profiling of DNA Breakage

Frontiers in Genetics ◽

10.3389/fgene.2020.610386 ◽

2021 ◽

Vol 11 ◽

Author(s):

Matthew J. Rybin ◽

Melina Ramic ◽

Natalie R. Ricciardi ◽

Philipp Kapranov ◽

Claes Wahlestedt ◽

...

Keyword(s):

Genome Instability ◽

Dna Double Strand Breaks ◽

Single Nucleotide ◽

Strand Breaks ◽

Single Strand Breaks ◽

Genome Wide ◽

A Genome ◽

Wide Scale ◽

Nucleotide Resolution ◽

Genomic Regions

Genome instability is associated with myriad human diseases and is a well-known feature of both cancer and neurodegenerative disease. Until recently, the ability to assess DNA damage—the principal driver of genome instability—was limited to relatively imprecise methods or restricted to studying predefined genomic regions. Recently, new techniques for detecting DNA double strand breaks (DSBs) and single strand breaks (SSBs) with next-generation sequencing on a genome-wide scale with single nucleotide resolution have emerged. With these new tools, efforts are underway to define the “breakome” in normal aging and disease. Here, we compare the relative strengths and weaknesses of these technologies and their potential application to studying neurodegenerative diseases.

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