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Current Opinion in Genetics &... Jun 2023The organization of the genome into euchromatin and heterochromatin has been known for almost 100 years [1]. More than 50% of mammalian genomes contain repetitive... (Review)
Review
The organization of the genome into euchromatin and heterochromatin has been known for almost 100 years [1]. More than 50% of mammalian genomes contain repetitive sequences [2,3]. Recently, a functional link between the genome and its folding has been identified [4,5]. Homotypic clustering of long interspersed nuclear element 1 (LINE1 or L1) and B1/Alu retrotransposons forms grossly exclusive nuclear domains that characterize and predict heterochromatin and euchromatin, respectively. The spatial segregation of L1 and B1/Alu-rich compartments is conserved in mammalian cells and can be rebuilt during the cell cycle and established de novo in early embryogenesis. Inhibition of L1 RNA drastically weakened homotypic repeat contacts and compartmental segregation, indicating that L1 plays a more significant role than just being a compartmental marker. This simple and inclusive genetic coding model of L1 and B1/Alu in shaping the macroscopic structure of the genome provides a plausible explanation for the remarkable conservation and robustness of its folding in mammalian cells. It also proposes a conserved core structure on which subsequent dynamic regulation takes place.
Topics: Animals; Heterochromatin; Euchromatin; Repetitive Sequences, Nucleic Acid; Long Interspersed Nucleotide Elements; Retroelements; Alu Elements; Mammals
PubMed: 37229928
DOI: 10.1016/j.gde.2023.102049 -
G3 (Bethesda, Md.) Mar 2022Repetitive sequences including transposable elements and transposon-derived fragments account for nearly half of the human genome. While transposition-competent...
Repetitive sequences including transposable elements and transposon-derived fragments account for nearly half of the human genome. While transposition-competent transposable elements must be repressed to maintain genomic stability, mutated and fragmented transposable elements comprising the bulk of repetitive sequences can also contribute to regulation of host gene expression and broader genome organization. Here, we analyzed published ChIP-seq data sets to identify proteins broadly enriched on transposable elements in the human genome. We show 2 of the proteins identified, C2H2 zinc finger-containing proteins ZNF146 (also known as OZF) and ZNF507, are targeted to distinct sites within LINE-1 ORF2 at thousands of locations in the genome. ZNF146 binding sites are found at old and young LINE-1 elements. In contrast, ZNF507 preferentially binds at young LINE-1 sequences correlated to sequence changes in LINE-1 elements at ZNF507's binding site. To gain further insight into ZNF146 and ZNF507 function, we disrupt their expression in HEK293 cells using CRISPR/Cas9 and perform RNA sequencing, finding modest gene expression changes in cells where ZNF507 has been disrupted. We further identify a physical interaction between ZNF507 and PRMT5, suggesting ZNF507 may target arginine methylation activity to LINE-1 sequences.
Topics: Binding Sites; DNA Transposable Elements; Genome, Human; HEK293 Cells; Humans; Kruppel-Like Transcription Factors; Long Interspersed Nucleotide Elements; Protein-Arginine N-Methyltransferases; RNA-Binding Proteins
PubMed: 35100360
DOI: 10.1093/g3journal/jkac002 -
Cells Aug 2022The main roles of placentas include physical protection, nutrient and oxygen import, export of gasses and fetal waste products, and endocrinological regulation. In... (Review)
Review
The main roles of placentas include physical protection, nutrient and oxygen import, export of gasses and fetal waste products, and endocrinological regulation. In addition to physical protection of the fetus, the placentas must provide immune protection throughout gestation. These basic functions are well-conserved; however, placentas are undoubtedly recent evolving organs with structural and cellular diversities. These differences have been explained for the last two decades through co-opting genes and gene control elements derived from transposable elements, including endogenous retroviruses (ERVs). However, the differences in placental structures have not been explained or characterized. This manuscript addresses the sorting of ERVs and their integration into the mammalian genomes and provides new ways to explain why placental structures have diverged.
Topics: Animals; DNA Transposable Elements; Endogenous Retroviruses; Female; Mammals; Placenta; Pregnancy
PubMed: 35954303
DOI: 10.3390/cells11152458 -
Viruses Jan 2021Although mobile genetic elements, or transposons, have played an important role in genome evolution, excess activity of mobile elements can have detrimental... (Review)
Review
Although mobile genetic elements, or transposons, have played an important role in genome evolution, excess activity of mobile elements can have detrimental consequences. Already, the enhanced expression of transposons-derived nucleic acids can trigger autoimmune reactions that may result in severe autoinflammatory disorders. Thus, cells contain several layers of protective measures to restrict transposons and to sense the enhanced activity of these "intragenomic pathogens". This review focuses on our current understanding of immunogenic patterns derived from the most active elements in humans, the retrotransposons long interspersed element (LINE)-1 and Alu. We describe the role of known pattern recognition receptors in nucleic acid sensing of LINE-1 and Alu and the possible consequences for autoimmune diseases.
Topics: Alu Elements; Animals; Disease Susceptibility; Genetic Predisposition to Disease; Host-Pathogen Interactions; Humans; Long Interspersed Nucleotide Elements; Retroelements
PubMed: 33445593
DOI: 10.3390/v13010094 -
Nature Microbiology Nov 2022Argonaute (Ago) proteins are found in all three domains of life. The so-called long Agos are composed of four major domains (N, PAZ, MID and PIWI) and contribute to RNA...
Argonaute (Ago) proteins are found in all three domains of life. The so-called long Agos are composed of four major domains (N, PAZ, MID and PIWI) and contribute to RNA silencing in eukaryotes (eAgos) or defence against invading mobile genetic elements in prokaryotes (pAgos). The majority (~60%) of pAgos identified bioinformatically are shorter (comprising only MID and PIWI domains) and are typically associated with Sir2, Mrr or TIR domain-containing proteins. The cellular function and mechanism of short pAgos remain enigmatic. Here we show that Geobacter sulfurreducens short pAgo and the NAD-bound Sir2 protein form a stable heterodimeric complex. The GsSir2/Ago complex presumably recognizes invading plasmid or phage DNA and activates the Sir2 subunit, which triggers endogenous NAD depletion and cell death, and prevents the propagation of invading DNA. We reconstituted NAD depletion activity in vitro and showed that activated GsSir2/Ago complex functions as a NADase that hydrolyses NAD to ADPR. Thus, short Sir2-associated pAgos provide defence against phages and plasmids, underscoring the diversity of mechanisms of prokaryotic Agos.
Topics: NAD; Prokaryotic Cells; Argonaute Proteins; DNA; Bacteriophages; Interspersed Repetitive Sequences
PubMed: 36192537
DOI: 10.1038/s41564-022-01239-0 -
Genes Mar 2023Social diversification in microbes is an evolutionary process where lineages bifurcate into distinct populations that cooperate with themselves but not with other... (Review)
Review
Social diversification in microbes is an evolutionary process where lineages bifurcate into distinct populations that cooperate with themselves but not with other groups. In bacteria, this is frequently driven by horizontal transfer of mobile genetic elements (MGEs). Here, the resulting acquisition of new genes changes the recipient's social traits and consequently how they interact with kin. These changes include discriminating behaviors mediated by newly acquired effectors. Since the producing cell is protected by cognate immunity factors, these selfish elements benefit from selective discrimination against recent ancestors, thus facilitating their proliferation and benefiting the host. Whether social diversification benefits the population at large is less obvious. The widespread use of next-generation sequencing has recently provided new insights into population dynamics in natural habitats and the roles MGEs play. MGEs belong to accessory genomes, which often constitute the majority of the pangenome of a taxon, and contain most of the kin-discriminating loci that fuel rapid social diversification. We further discuss mechanisms of diversification and its consequences to populations and conclude with a case study involving myxobacteria.
Topics: Bacteria; Myxococcales; Biological Evolution; Genome; Interspersed Repetitive Sequences
PubMed: 36980919
DOI: 10.3390/genes14030648 -
International Journal of Medical... May 2020Pasteurella multocida is an important veterinary pathogen able to infect a wide range of animals in a broad spectrum of diseases. P. multocida is a complex microorganism... (Review)
Review
Pasteurella multocida is an important veterinary pathogen able to infect a wide range of animals in a broad spectrum of diseases. P. multocida is a complex microorganism in relation to its genomic flexibility, host adaptation and pathogenesis. Epidemiological analysis based on multilocus sequence typing, serotyping, genotyping, association with virulence genes and single nucleotide polymorphisms (SNPs), enables assessment of intraspecies diversity, phylogenetic and strain-specific relationships associated with host predilection or disease. A high number of sequenced genomes provides us a more accurate genomic and epidemiological interpretation to determine whether certain lineages can infect a host or produce disease. Comparative genomic analysis and pan-genomic approaches have revealed a flexible genome for hosting mobile genetic elements (MGEs) and therefore significant variation in gene content. Moreover, it was possible to find lineage-specific MGEs from the same niche, showing acquisition probably due to an evolutionary convergence event or to a genetic group with infective capacity. Furthermore, diversification selection analysis exhibits proteins exposed on the surface subject to selection pressures with an interstrain heterogeneity related to their ability to adapt. This article is the first review describing the genomic relationship to elucidate the diversity and evolution of P. multocida.
Topics: Adaptation, Physiological; Animals; Evolution, Molecular; Genetic Variation; Genome, Bacterial; Genomics; Humans; Interspersed Repetitive Sequences; Pasteurella Infections; Pasteurella multocida; Phylogeny; Polymorphism, Single Nucleotide; Poultry; Virulence
PubMed: 32276876
DOI: 10.1016/j.ijmm.2020.151417 -
Current Genetics Dec 2020Bacteria and other prokaryotes evolve primarily through rapid changes in their gene content by quickly losing and gaining genes whenever an ecological opportunity... (Review)
Review
Bacteria and other prokaryotes evolve primarily through rapid changes in their gene content by quickly losing and gaining genes whenever an ecological opportunity emerges. As gene loss and horizontal gene transfer (HGT) appear to be the most common events across the prokaryotic tree of life, we need to think beyond gradual sequence evolution if we wish to understand the microbial world. Especially genes that reside on mobile genetic elements (MGEs) may spread much more rapidly through a microbial population than genes that reside on the bacterial chromosome. This raises the question: why are some genes associated with MGEs, while others are not? Here, I briefly review a recently proposed class of genes for which we have coined the term "rescuable genes". The fitness effect of carrying these genes is so small, either constantly or on average, that they are prone to be lost from a microbial population. I argue that HGT, even when costly to the individual cells, may play an important role in maintaining these rescuable genes in microbial communities.
Topics: Bacteria; Chromosomes, Bacterial; Evolution, Molecular; Gene Transfer, Horizontal; Interspersed Repetitive Sequences; Prokaryotic Cells
PubMed: 32880674
DOI: 10.1007/s00294-020-01104-9 -
Analytical Biochemistry Oct 2020
Topics: Animals; DNA Transposable Elements; Evolution, Molecular; Genome Size; Humans; Long Interspersed Nucleotide Elements; MicroRNAs; Short Interspersed Nucleotide Elements
PubMed: 32730813
DOI: 10.1016/j.ab.2020.113888 -
The Journal of Antimicrobial... Sep 2022The oxazolidinones (linezolid and tedizolid) are last-resort antimicrobial agents used for the treatment of severe infections in humans caused by MDR Gram-positive... (Review)
Review
The oxazolidinones (linezolid and tedizolid) are last-resort antimicrobial agents used for the treatment of severe infections in humans caused by MDR Gram-positive bacteria. They bind to the peptidyl transferase centre of the bacterial ribosome inhibiting protein synthesis. Even if the majority of Gram-positive bacteria remain susceptible to oxazolidinones, resistant isolates have been reported worldwide. Apart from mutations, affecting mostly the 23S rDNA genes and selected ribosomal proteins, acquisition of resistance genes (cfr and cfr-like, optrA and poxtA), often associated with mobile genetic elements [such as non-conjugative and conjugative plasmids, transposons, integrative and conjugative elements (ICEs), prophages and translocatable units], plays a critical role in oxazolidinone resistance. In this review, we briefly summarize the current knowledge on oxazolidinone resistance mechanisms and provide an overview on the diversity of the mobile genetic elements carrying oxazolidinone resistance genes in Gram-positive and Gram-negative bacteria.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; DNA, Ribosomal; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Interspersed Repetitive Sequences; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Peptidyl Transferases; Ribosomal Proteins
PubMed: 35989417
DOI: 10.1093/jac/dkac263