scholarly journals DNA methylation enables transposable element-driven genome expansion

2020 ◽  
Vol 117 (32) ◽  
pp. 19359-19366
Author(s):  
Wanding Zhou ◽  
Gangning Liang ◽  
Peter L. Molloy ◽  
Peter A. Jones
Keyword(s):  
Cytosine Methylation ◽  
Host Genome ◽  
Substantial Part ◽  
Gene Control ◽  
Cytosine Deamination ◽  
Transcription Start Sites ◽  
Genome Expansion ◽  
A Genome ◽  
Cpg Dinucleotide ◽  
Regulatory Functions

Multicellular eukaryotic genomes show enormous differences in size. A substantial part of this variation is due to the presence of transposable elements (TEs). They contribute significantly to a cell’s mass of DNA and have the potential to become involved in host gene control. We argue that the suppression of their activities by methylation of the C–phosphate–G (CpG) dinucleotide in DNA is essential for their long-term accommodation in the host genome and, therefore, to its expansion. An inevitable consequence of cytosine methylation is an increase in C-to-T transition mutations via deamination, which causes CpG loss. Cytosine deamination is often needed for TEs to take on regulatory functions in the host genome. Our study of the whole-genome sequences of 53 organisms showed a positive correlation between the size of a genome and the percentage of TEs it contains, as well as a negative correlation between size and the CpG observed/expected (O/E) ratio in both TEs and the host DNA. TEs are seldom found at promoters and transcription start sites, but they are found more at enhancers, particularly after they have accumulated C-to-T and other mutations. Therefore, the methylation of TE DNA allows for genome expansion and also leads to new opportunities for gene control by TE-based regulatory sites.

scholarly journals The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 172 ◽  
Author(s):  
Hemant Gujar ◽  
Daniel Weisenberger ◽  
Gangning Liang
Keyword(s):  
Dna Methylation ◽  
Cytosine Methylation ◽  
De Novo ◽  
Ring Finger ◽  
Dna Methyltransferases ◽  
Epigenetic Modifications ◽  
Hard Copy ◽  
Physiological Processes ◽  
New Gene ◽  
Cpg Dinucleotide

A DNA sequence is the hard copy of the human genome and it is a driving force in determining the physiological processes in an organism. Concurrently, the chemical modification of the genome and its related histone proteins is dynamically involved in regulating physiological processes and diseases, which overall constitutes the epigenome network. Among the various forms of epigenetic modifications, DNA methylation at the C-5 position of cytosine in the cytosine–guanine (CpG) dinucleotide is one of the most well studied epigenetic modifications. DNA methyltransferases (DNMTs) are a family of enzymes involved in generating and maintaining CpG methylation across the genome. In mammalian systems, DNA methylation is performed by DNMT1 and DNMT3s (DNMT3A and 3B). DNMT1 is predominantly involved in the maintenance of DNA methylation during cell division, while DNMT3s are involved in establishing de novo cytosine methylation and maintenance in both embryonic and somatic cells. In general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on the role of DNMT3B and its isoforms in de novo methylation and maintenance of DNA methylation, especially with respect to their role as an accessory protein.

scholarly journals Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to modulate chromatin structure and gene expression

2018 ◽  
Author(s):  
Mary Miyaji ◽  
Ryohei Furuta ◽  
Osamu Hosoya ◽  
Kuniaki Sano ◽  
Norikazu Hara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Model Building ◽  
Mapping Technique ◽  
Dna Duplexes ◽  
Transcription Start Sites ◽  
A Genome ◽  
Topo Ii ◽  
Type Ii Dna Topoisomerases ◽  
Strand Passage

AbstractBackgroundType II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T-segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be placed far from each other on the same chromosome. However, no direct evidence for this to occur has been described so far due to lack of proper methodology.ResultsThe beta isoform of topo II (topo IIβ) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. To elucidate the enzyme’s role in the process, here we devise a genome-wide mapping technique for topo IIβ target sites that can measure the genomic distance between G- and T-segments. It became clear that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that the DSP sites are intertwined or knotted and topo IIβ is engaged in unknotting reaction that leads to chromatin decondensation and gene regulation.ConclusionsWhen combined with categorized gene expression analysis, the model-based prediction of DSP sites reveals that DSP is one of the key factors for topo IIβ-dependency of neuronal gene regulation.

scholarly journals Genome expansion by allopolyploidization in the fungal strain Coniochaeta 2T2.1 and its exceptional lignocellulolytic machinery

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Stephen J. Mondo ◽  
Diego Javier Jiménez ◽  
Ronald E. Hector ◽  
Anna Lipzen ◽  
Mi Yan ◽  
...  
Keyword(s):  
Wheat Straw ◽  
Purifying Selection ◽  
Reticulate Evolution ◽  
Phylogenomic Analysis ◽  
Lignocellulolytic Enzymes ◽  
Genome Expansion ◽  
Lack Of Information ◽  
Genome Wide ◽  
A Genome ◽  
Furanic Compounds

Abstract Background Particular species of the genus Coniochaeta (Sordariomycetes) exhibit great potential for bioabatement of furanic compounds and have been identified as an underexplored source of novel lignocellulolytic enzymes, especially Coniochaeta ligniaria. However, there is a lack of information about their genomic features and metabolic capabilities. Here, we report the first in-depth genome/transcriptome survey of a Coniochaeta species (strain 2T2.1). Results The genome of Coniochaeta sp. strain 2T2.1 has a size of 74.53 Mbp and contains 24,735 protein-encoding genes. Interestingly, we detected a genome expansion event, resulting ~ 98% of the assembly being duplicated with 91.9% average nucleotide identity between the duplicated regions. The lack of gene loss, as well as the high divergence and strong genome-wide signatures of purifying selection between copies indicates that this is likely a recent duplication, which arose through hybridization between two related Coniochaeta-like species (allopolyploidization). Phylogenomic analysis revealed that 2T2.1 is related Coniochaeta sp. PMI546 and Lecythophora sp. AK0013, which both occur endophytically. Based on carbohydrate-active enzyme (CAZy) annotation, we observed that even after in silico removal of its duplicated content, the 2T2.1 genome contains exceptional lignocellulolytic machinery. Moreover, transcriptomic data reveal the overexpression of proteins affiliated to CAZy families GH11, GH10 (endoxylanases), CE5, CE1 (xylan esterases), GH62, GH51 (α-l-arabinofuranosidases), GH12, GH7 (cellulases), and AA9 (lytic polysaccharide monoxygenases) when the fungus was grown on wheat straw compared with glucose as the sole carbon source. Conclusions We provide data that suggest that a recent hybridization between the genomes of related species may have given rise to Coniochaeta sp. 2T2.1. Moreover, our results reveal that the degradation of arabinoxylan, xyloglucan and cellulose are key metabolic processes in strain 2T2.1 growing on wheat straw. Different genes for key lignocellulolytic enzymes were identified, which can be starting points for production, characterization and/or supplementation of enzyme cocktails used in saccharification of agricultural residues. Our findings represent first steps that enable a better understanding of the reticulate evolution and “eco-enzymology” of lignocellulolytic Coniochaeta species.

Cytosine Methylation Is Not the Major Factor Inducing CpG Dinucleotide Deficiency in Bacterial Genomes

2004 ◽  
Vol 58 (6) ◽  
pp. 692-700 ◽  
Author(s):  
Yong Wang ◽  
Eduardo P.C. Rocha ◽  
Frederick C.C. Leung ◽  
Antoine Danchin
Keyword(s):  
Cytosine Methylation ◽  
Bacterial Genomes ◽  
Cpg Dinucleotide

scholarly journals An optimized ChIP-Seq framework for profiling of histone modifications in Chromochloris zofingiensis

2021 ◽  
Author(s):  
Daniela Strenkert ◽  
Matthew Mingay ◽  
Stefan Schmollinger ◽  
Cindy Chen ◽  
Ronan C O'Malley ◽  
...  
Keyword(s):  
Fragment Size ◽  
Transcriptome Profiling ◽  
Formaldehyde Concentration ◽  
Structural Annotation ◽  
Transcription Start Sites ◽  
Genome Wide ◽  
Chip Experiment ◽  
A Genome ◽  
Dna Shearing ◽  
Chromochloris Zofingiensis

The eukaryotic green alga Chromochloris zofingiensis is a reference organism for studying carbon partitioning and a promising candidate for the production of biofuel precursors. Recent transcriptome profiling transformed our understanding of its biology and generally algal biology, but epigenetic regulation remains understudied and represents a fundamental gap in our understanding of algal gene expression. Chromatin Immunoprecipitation followed by deep sequencing (ChIP-Seq) is a powerful tool for the discovery of such mechanisms, by identifying genome-wide histone modification patterns and transcription factor-binding sites alike. Here, we established a ChIP-Seq framework for Chr. zofingiensis yielding over 20 million high quality reads per sample. The most critical steps in a ChIP experiment were optimized, including DNA shearing to obtain an average DNA fragment size of 250 bp and assessment of the recommended formaldehyde concentration for optimal DNA-protein crosslinking. We used this ChIP-Seq framework to generate a genome-wide map of the H3K4me3 distribution pattern and to integrate these data with matching RNA-Seq data. In line with observations from other organisms, H3K4me3 marks predominantly transcription start sites of genes. Our H3K4me3 ChIP-Seq data will pave the way for improved genome structural annotation in the emerging reference alga Chr. zofingiensis.

scholarly journals The major mechanism of melanoma mutations is based on deamination of cytosine in pyrimidine dimers as determined by circle damage sequencing

2021 ◽  
Vol 7 (31) ◽  
pp. eabi6508
Author(s):  
Seung-Gi Jin ◽  
Dean Pettinga ◽  
Jennifer Johnson ◽  
Peipei Li ◽  
Gerd P. Pfeifer
Keyword(s):  
Sequence Specificity ◽  
Uvb Radiation ◽  
Cyclobutane Pyrimidine Dimers ◽  
Sequence Context ◽  
Cytosine Deamination ◽  
Transcription Start Sites ◽  
Major Mechanism ◽  
Pyrimidine Dimers ◽  
Genome Wide

Sunlight-associated melanomas carry a unique C-to-T mutation signature. UVB radiation induces cyclobutane pyrimidine dimers (CPDs) as the major form of DNA damage, but the mechanism of how CPDs cause mutations is unclear. To map CPDs at single-base resolution genome wide, we developed the circle damage sequencing (circle-damage-seq) method. In human cells, CPDs form preferentially in a tetranucleotide sequence context (5′-Py-T<>Py-T/A), but this alone does not explain the tumor mutation patterns. To test whether mutations arise at CPDs by cytosine deamination, we specifically mapped UVB-induced cytosine-deaminated CPDs. Transcription start sites (TSSs) were protected from CPDs and deaminated CPDs, but both lesions were enriched immediately upstream of the TSS, suggesting a mutation-promoting role of bound transcription factors. Most importantly, the genomic dinucleotide and trinucleotide sequence specificity of deaminated CPDs matched the prominent mutation signature of melanomas. Our data identify the cytosine-deaminated CPD as the leading premutagenic lesion responsible for mutations in melanomas.

scholarly journals An introgressed gene causes meiotic drive in Neurospora sitophila

2020 ◽  
Author(s):  
Jesper Svedberg ◽  
Aaron A. Vogan ◽  
Nicholas A. Rhoades ◽  
Dilini Sarmarajeewa ◽  
David J. Jacobson ◽  
...  
Keyword(s):  
Rna Interference ◽  
Natural Populations ◽  
Meiotic Drive ◽  
Host Genome ◽  
Origin And Evolution ◽  
Filamentous Ascomycete ◽  
Selfish Genes ◽  
A Genome ◽  
Spore Killing ◽  
Spore Killer

AbstractMeiotic drive elements cause their own preferential transmission following meiosis. In fungi this phenomenon takes the shape of spore killing, and in the filamentous ascomycete Neurospora sitophila, the Sk-1 spore killer element is found in many natural populations. In this study, we identify the gene responsible for spore killing in Sk-1 by generating both long and short-read genomic data and by using these data to perform a genome wide association test. Through molecular dissection, we show that a single 405 nucleotide long open reading frame generates a product that both acts as a poison capable of killing sibling spores and as an antidote that rescues spores that produce it. By phylogenetic analysis, we demonstrate that the gene is likely to have been introgressed from the closely related species N. hispaniola, and we identify three subclades of N. sitophila, one where Sk-1 is fixed, another where Sk-1 is absent, and a third where both killer and sensitive strain are found. Finally, we show that spore killing can be suppressed through an RNA interference based genome defense pathway known as meiotic silencing by unpaired DNA. Spk-1 is not related to other known meiotic drive genes, and similar sequences are only found within Neurospora. These results shed new light on the diversity of genes capable of causing meiotic drive, their origin and evolution and their interaction with the host genome.Significance StatementIn order to survive, most organisms have to deal with parasites. Such parasites can be other organisms, or sometimes, selfish genes found within the host genome itself. While much is known about parasitic organisms, the interaction with their hosts and their ability to spread within and between species, much less is known about selfish genes. We here identify a novel selfish “spore killer” gene in the fungus Neurospora sitophila. The gene appears to have evolved within the genus, but has entered the species through hybridization and introgression. We also show that the host can counteract the gene through RNA interference. These results shed new light on the diversity of selfish genes in terms of origin, evolution and host interactions.

scholarly journals Third-generation sequencing-based mapping and visualization of single nucleotide polymorphism, meiotic recombination, illegitimate mutation and repeat-induced point mutation

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Wan-Chen Li ◽  
Hou-Cheng Liu ◽  
Ying-Jyun Lin ◽  
Shu-Yun Tung ◽  
Ting-Fang Wang
Keyword(s):  
Point Mutation ◽  
Meiotic Recombination ◽  
Molecular Mechanisms ◽  
Cytosine Methylation ◽  
Defense Mechanism ◽  
Nucleotide Polymorphisms ◽  
Tetrad Analysis ◽  
Single Nucleotide ◽  
A Genome ◽  
Repeat Induced Point Mutation

Abstract Generation of new genetic diversity by crossover (CO) and non-crossover (NCO) is a fundamental process in eukaryotes. Fungi have played critical roles in studying this process because they permit tetrad analysis, which has been used by geneticists for several decades to determine meiotic recombination products. New genetic variations can also be generated in zygotes via illegitimate mutation (IM) and repeat-induced point mutation (RIP). RIP is a genome defense mechanism for preventing harmful expansion of transposable elements or duplicated sequences in filamentous fungi. Although the exact mechanism of RIP is unknown, the C:G to T:A mutations might result from DNA cytosine methylation. A comprehensive approach for understanding the molecular mechanisms underlying these important processes is to perform high-throughput mapping of CO, NCO, RIP and IM in zygotes bearing large numbers of heterozygous variant markers. To this aim, we developed ‘TSETA’, a versatile and user-friendly pipeline that utilizes high-quality and chromosome-level genome sequences involved in a single meiotic event of the industrial workhorse fungus Trichoderma reesei. TSETA not only can be applied to most sexual eukaryotes for genome-wide tetrad analysis, it also outcompetes most currently used methods for calling out single nucleotide polymorphisms between two or more intraspecies strains or isolates.

Sign in / Sign up

Export Citation Format

Share Document