TNRC18 engages H3K9me3 to mediate silencing of endogenous retrotransposons

Nature, Journal Year: 2023, Volume and Issue: 623(7987), P. 633 - 642

Published: Nov. 8, 2023

Trimethylation of histone H3 lysine 9 (H3K9me3) is crucial for the regulation gene repression and heterochromatin formation, cell-fate determination organismal development1. H3K9me3 also provides an essential mechanism silencing transposable elements1–4. However, previous studies have shown that canonical readers (for example, HP1 (refs. 5–9) MPP8 10–12)) limited roles in endogenous retroviruses (ERVs), one main element classes mammalian genome13. Here we report trinucleotide-repeat-containing 18 (TNRC18), a poorly understood chromatin regulator, recognizes to mediate ERV class I (ERV1) elements such as LTR12 (ref. 14). Biochemical, biophysical structural identified carboxy-terminal bromo-adjacent homology (BAH) domain TNRC18 (TNRC18(BAH)) H3K9me3-specific reader. Moreover, amino-terminal segment platform direct recruitment co-repressors HDAC–Sin3–NCoR complexes, thus enforcing optimal H3K9me3-demarcated ERVs. Point mutagenesis disrupts TNRC18(BAH)-mediated engagement caused neonatal death mice and, multiple cell models, led derepressed expression ERVs, which affected landscape cis-regulatory therefore, gene-expression programmes. Collectively, describe new H3K9me3-sensing regulatory pathway operates epigenetically silence evolutionarily young ERVs exert substantial effects on host genome integrity, transcriptomic regulation, immunity development. Trinucleotide-repeat-containing has functions, now reader silences retroviruses.

Language: Английский

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H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(7), P. 935 - 947

Published: June 12, 2023

Abstract Mammalian genomes harbor abundant transposable elements (TEs) and their remnants, with numerous epigenetic repression mechanisms enacted to silence TE transcription. However, TEs are upregulated during early development, neuronal lineage, cancers, although the factors contributing transcription of have yet be fully elucidated. Here, we demonstrate that male-specific lethal (MSL)-complex-mediated histone H4 acetylation at lysine 16 (H4K16ac) is enriched in human embryonic stem cells (hESCs) cancer cells. This turn activates subsets full-length long interspersed nuclear (LINE1s, L1s) endogenous retrovirus (ERV) terminal repeats (LTRs). Furthermore, show H4K16ac-marked L1 LTR subfamilies display enhancer-like functions genomic locations chromatin features associated active enhancers. Importantly, such regions often reside boundaries topologically domains loop genes. CRISPR-based perturbation genetic deletion L1s reveal LTRs regulate expression genes cis . Overall, H4K16ac contribute -regulatory landscape specific by maintaining an TEs.

Language: Английский

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Variation in mutation, recombination, and transposition rates inDrosophila melanogasterandDrosophila simulans

Genome Research, Journal Year: 2023, Volume and Issue: 33(4), P. 587 - 598

Published: April 1, 2023

The rates of mutation, recombination, and transposition are core parameters in models evolution. They impact genetic diversity, responses to ongoing selection, levels load. However, even for key evolutionary model species such as Drosophila melanogaster simulans, few estimates these available, we have little idea how vary between individuals, sexes, or populations. Knowledge this variation is fundamental parameterizing genome Here, provide direct their a West African European population D. simulans Across 89 flies, observe 58 single-nucleotide mutations, 286 crossovers, transposable element (TE) insertions. Compared the melanogaster, find has lower mutation rate (1.67 × 10-9 site-1 gen-1 vs. 4.86 gen-1) (8.99 10-5 copy-1 23.36 gen-1), but higher recombination (3.44 cM/Mb 2.06 cM/Mb). similar significantly lower, not different, rate. Overall, paternal-derived mutations more frequent than maternal ones both species. Our study quantifies among different populations our will benefit future studies genetics.

Language: Английский

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Major proliferation of transposable elements shaped the genome of the soybean rust pathogen Phakopsora pachyrhizi

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 1, 2023

Abstract With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, feature unique to in which two haploid nuclei reside same cell. A key example is Phakopsora pachyrhizi , causal agent Asian soybean disease, one world’s most economically damaging agricultural diseases. Despite P. ’s impact, exceptional size complexity its genome prevented generation an accurate assembly. Here, we sequence three independent genomes uncover up 1.25 Gb comprising haplotypes with transposable element (TE) content ~93%. We study incursion dominant these TEs show how they have various processes such as host range adaptation, stress responses genetic plasticity.

Language: Английский

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The Dynamic Interplay Between Ribosomal DNA and Transposable Elements: A Perspective From Genomics and Cytogenetics

Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(3)

Published: Feb. 2, 2024

Abstract Although both are salient features of genomes, at first glance ribosomal DNAs and transposable elements genetic with not much in common: whereas mainly viewed as housekeeping genes that uphold all prime genome functions, generally portrayed selfish disruptive. These opposing characteristics also mirrored other attributes: organization tandem (ribosomal DNAs) versus a dispersed manner (transposable elements); evolution concerted by diversification activity prolongs genomic stability shortens it elements). Re-visiting relevant instances which DNA–transposable element interactions have been reported, we note repeat types share least four structural functional hallmarks: (1) they repetitive shape genomes evolutionary timescales, (2) exchange motifs can enter co-evolution processes, (3) tightly controlled stress sensors playing key roles senescence/aging, (4) common epigenetic marks such DNA methylation histone modification. Here, give an overview the structural, functional, elements, discuss their interactions, highlight trends future directions move forward understanding associations.

Language: Английский

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A genome-wide study of ruminants uncovers two endogenous retrovirus families recently active in goats

Mobile DNA, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 17, 2025

Endogenous retroviruses (ERV) are traces of ancestral retroviral germline infections that constitute a significant portion mammalian genomes and classified as LTR-retrotransposons. The exploration their dynamics evolutionary history in ruminants remains limited, highlighting the need for comprehensive thorough investigation ERV landscape cattle, sheep goat. Through de novo bioinformatic analysis, we characterized 24 Class I II families across four reference assemblies domestic wild goats, one assembly cattle. Among these families, 13 represented by consensus sequences identified five analyzed species, while eight exclusive to small three similarity-based approach used search presence other ruminant species revealed multiple endogenization events over last 40 million years distinct among species. annotation resulted high-resolution dataset 100,534 insertions genomes, representing between 0.5 1% genomes. Solo-LTRs account 83.2% annotated demonstrating most ERVs relics past events. Two showed higher abundance copy conservation ruminants. One them is closely related circulating exogenous 22 copies sharing identical LTRs 12 with complete coding capacities Our results suggest two recent transpositional activity particularly goat, illustrating This work highlights ongoing influence on genomic landscapes call further trajectories

Language: Английский

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Causes and consequences of linkage disequilibrium among transposable elements within eukaryotic genomes

Genetics, Journal Year: 2023, Volume and Issue: 224(2)

Published: April 6, 2023

Abstract Sex and recombination can affect the dynamics of transposable elements (TEs) in various ways: while sex is expected to help TEs spread within populations, deleterious effect ectopic among transposons represents a possible source purifying selection limiting their number. Furthermore, may also increase efficiency against by reducing selective interference loci. In order better understand effects reproductive systems on TE dynamics, this article provides analytical expressions for linkage disequilibrium classical model which number stabilized synergistic selection. The results show that positive predicted infinite populations despite negative epistasis, due transposition process. Positive substantially inflate variance per genome case partially selfing or clonal populations. Finite population size tends generate (Hill–Robertson effect), relative importance increasing with degree then extended explore how recombination. While generated generally disfavors recombination, Hill–Robertson represent non-negligible indirect when are abundant. However, direct fitness cost imposed drives towards low-recombination regimes, at cannot be maintained stable equilibrium.

Language: Английский

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HiTE: a fast and accurate dynamic boundary adjustment approach for full-length transposable element detection and annotation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 2, 2024

Abstract Recent advancements in genome assembly have greatly improved the prospects for comprehensive annotation of Transposable Elements (TEs). However, existing methods TE using assemblies suffer from limited accuracy and robustness, requiring extensive manual editing. In addition, currently available gold-standard databases are not comprehensive, even extensively studied species, highlighting critical need an automated detection method to supplement repositories. this study, we introduce HiTE, a fast accurate dynamic boundary adjustment approach designed detect full-length TEs. The experimental results demonstrate that HiTE outperforms RepeatModeler2, state-of-the-art tool, across various species. Furthermore, has identified numerous novel transposons with well-defined structures containing protein-coding domains, some which directly inserted within crucial genes, leading direct alterations gene expression. A Nextflow version is also available, enhanced parallelism, reproducibility, portability.

Language: Английский

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Jump-starting life: balancing transposable element co-option and genome integrity in the developing mammalian embryo

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(4), P. 1721 - 1733

Published: March 25, 2024

Abstract Remnants of transposable elements (TEs) are widely expressed throughout mammalian embryo development. Originally infesting our genomes as selfish and acting a source genome instability, several these have been co-opted part complex system regulation. Many TEs lost transposition ability their transcriptional potential has tampered result interactions with the host evolutionary time. It proposed that ultimately repurposed to function gene regulatory hubs scattered genomes. In early in particular, find perfect environment naïve chromatin escape repression by host. As consequence, it is thought hosts found ways co-opt TE sequences regulate large-scale changes transcription state this review, we discuss examples during development, for co-option regulation pressures on

Language: Английский

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Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3741 - 3760.e30

Published: June 5, 2024

Language: Английский

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