Diverse CGG binding proteins across eukaryotes produced by independent domestications of hAT transposons
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PROVIDER: PRJNA660048 | ENA |
REPOSITORIES: ENA
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Project description:The human transcription factor (TF) CGGBP1 (“CGG Binding Protein”) is conserved only in amniotes, and is believed to derive from the zf-BED and Hermes transposase DNA-binding domains (DBDs) of a hAT DNA transposon. Here, we examine the DNA binding preferences of a wide variety of metazoan CGGBP1-like TFs with this bipartite domain using PBM experiments. The derived motifs are available at ...
2021-02-09 | GSE157085 | GEO
Project description:The human transcription factor (TF) CGGBP1 (CGG-binding protein) is conserved only in amniotes and is believed to derive from the zf-BED and Hermes transposase DNA-binding domains (DBDs) of a hAT DNA transposon. Here, we show that sequence-specific DNA-binding proteins with this bipartite domain structure have resulted from dozens of independent hAT domestications in different eukaryotic lineages. CGGBPs display a wide range of sequence specificity, usually including preferences for CGG or CGC trinucleotides, whereas some bind AT-rich motifs. The CGGBPs are almost entirely nonsyntenic, and their protein sequences, DNA-binding motifs, and patterns of presence or absence in genomes are uncharacteristic of ancestry via speciation. At least eight CGGBPs in the coelacanth Latimeria chalumnae bind distinct motifs, and the expression of the corresponding genes varies considerably across tissues, suggesting tissue-restricted function.
| S-EPMC8097297 | biostudies-literature
Project description:Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides because of imperfect repair of deaminated methylcytosines. Here, we extensively survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than a billion years ago exhibit clustered methylation, specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a regime of genomic sequence evolution that enriches CG dinucleotides and drives the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints. DNA methylation, RNA and nucleosome sequencing data for diverse eukaryotes
2014-03-13 | E-GEOD-46692 | biostudies-arrayexpress
Project description:Extensive small RNAs sequestration in diverse eukaryotes
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Project description:Transcribed CGG repeat expansions cause the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). CGG repeat RNAs sequester RNA-binding proteins (RBPs) into nuclear foci and undergo repeat-associated non-AUG (RAN) translation into toxic peptides in the cytoplasm. To identify proteins involved in these processes, we employed a CGG repeat RNA-tagging system to capture repeat associated RBPs by mass spectrometry in mammalian cells. We identified several SR (serine/arginine-rich domain) proteins that interact selectively with CGG repeats basally and under cellular stress. These same proteins modify toxicity in a Drosophila model of FXTAS. Genetic or pharmacological targeting of serine/arginine protein kinases (SRPKs) inhibits RAN translation in cells and toxicity in both FXTAS and C9orf72 ALS/FTD model flies. Furthermore, SRPK inhibitors suppressed CGG repeat toxicity in rodent neurons. These findings demonstrate roles for CGG repeat RNA binding proteins in repeat toxicity and support further evaluation of SRPK inhibitors in modulating RAN translation associated with repeat expansion disorders.
2021-09-28 | PXD027000 | Pride
Project description:All eukaryotic DNA transposons reported so far belong to a single category of elements transposed by the so-called "cut-and-paste" mechanism. Here, we report a previously unknown category of eukaryotic DNA transposons, Helitron, which transpose by rolling-circle replication. Autonomous Helitrons encode a 5'-to-3' DNA helicase and nuclease/ligase similar to those encoded by known rolling-circle replicons. Helitron-like transposons have conservative 5'-TC and CTRR-3' termini and do not have terminal inverted repeats. They contain 16- to 20-bp hairpins separated by 10--12 nucleotides from the 3'-end and transpose precisely between the 5'-A and T-3', with no modifications of the AT target sites. Together with their multiple diverged nonautonomous descendants, Helitrons constitute approximately 2% of both the Arabidopsis thaliana and Caenorhabditis elegans genomes and also colonize the Oriza sativa genome. Sequence conservation suggests that Helitrons continue to be transposed.
| S-EPMC37501 | biostudies-literature
Project description:Fragile X syndrome (FXS) is a neurodevelopmental disorder and a leading cause of intellectual disability. In FXS, the neuronal regulator, FMR1, is epigenetically silenced by a CGG repeat expansion. Here, we investigate conditions under which repeat expansion and gene silencing could be reversed. Surprisingly, inducing formation of R-loops (3-stranded RNA-DNA structures) within FMR1 is sufficient to initiate CGG contraction, promoter demethylation, and FMR1 reactivation. Recruiting RNaseH degrades the R-loop and abolishes the response. Targeting the nascent mRNA for degradation also eliminates the response. Thus, we have identified an exogenous nuclease-free method of contracting CGG repeats and reversing FMR1 silencing. We propose that DNA demethylation, new transcription, and R-loop formation engage in a feed-forward cycle to contract CGG repeats and reactivate FMR1.
2023-05-19 | GSE184580 | GEO
Project description:Eukaryotes contain numerous transposable or mobile elements capable of parasite-like proliferation in the host genome. All known transposable elements in eukaryotes belong to two types: retrotransposons and DNA transposons. Here we report a previously uncharacterized class of DNA transposons called Polintons that populate genomes of protists, fungi, and animals, including entamoeba, soybean rust, hydra, sea anemone, nematodes, fruit flies, beetle, sea urchin, sea squirt, fish, lizard, frog, and chicken. Polintons from all these species are characterized by a unique set of proteins necessary for their transposition, including a protein-primed DNA polymerase B, retroviral integrase, cysteine protease, and ATPase. In addition, Polintons are characterized by 6-bp target site duplications, terminal-inverted repeats that are several hundred nucleotides long, and 5'-AG and TC-3' termini. Analogously to known transposable elements, Polintons exist as autonomous and nonautonomous elements. Our data suggest that Polintons have evolved from a linear plasmid that acquired a retroviral integrase at least 1 billion years ago. According to the model of Polinton transposition proposed here, a Polinton DNA molecule excised from the genome serves as a template for extrachromosomal synthesis of its double-stranded DNA copy by the Polinton-encoded DNA polymerase and is inserted back into genome by its integrase.
| S-EPMC1450207 | biostudies-literature
Project description:UnlabelledBackgroundMiniature inverted-repeat transposable elements (MITEs) are short, nonautonomous DNA elements flanked by subterminal or terminal inverted repeats (TIRs) with no coding capacity. MITEs were originally recognized as important components of plant genomes, where they can attain extremely high copy numbers, and are also found in several animal genomes, including mosquitoes, fish and humans. So far, few MITEs have been described in Drosophila.ResultsHerein we describe the distribution and evolution of Mar, a MITE family of hAT transposons, in Drosophilidae species. In silico searches and PCR screening showed that Mar distribution is restricted to the willistoni subgroup of the Drosophila species, and a phylogenetic analysis of Mar indicates that this element may have originated prior to the diversification of these species. Most of the Mar copies in D. willistoni present conserved target site duplications and TIRs, indicating recent mobilization of these sequences. We also identified relic copies of potentially full-length Mar transposon in D. tropicalis and D. willistoni. The phylogenetic relationship among transposases from the putative full-length Mar and other hAT superfamily elements revealed that Mar is placed into the recently determined Buster group of hAT transposons.ConclusionOn the basis of the obtained data, we can suggest that the origin of these Mar MITEs occurred before the subgroup willistoni speciation, which started about 5.7 Mya. The Mar relic transposase existence indicates that these MITEs originated by internal deletions and suggests that the full-length transposon was recently functional in D. willistoni, promoting Mar MITEs mobilization.
| S-EPMC3517528 | biostudies-literature