bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/338582

H3K9me3 is Required for Transgenerational Inheritance of Small RNAs that Target a Unique Subset of Newly Evolved Genes

Lev, I.·Gingold, H.·Rechavi, O.
View original source ↗Export metadata ↓

Abstract

In Caenorhabditis elegans, RNA interference (RNAi) responses can transmit across generations via small RNAs. RNAi inheritance is associated with Histone-3-Lysine-9 tri-methylation (H3K9me3) of the targeted genes. In other organisms, maintenance of silencing requires a feed-forward loop between H3K9me3 and small RNAs. Here we show that in C. elegans not only is H3K9me3 unnecessary for inheritance, the modifications function depends on the identity of the RNAi-targeted gene. We found an asymmetry in the requirement for H3K9me3 and the main worm H3K9me3 methyltransferases, SET-25 and SET-32. Both methyltransferases promote heritable silencing of the foreign gene gfp, but are dispensable for silencing of the endogenous gene oma-1. Genome-wide examination of heritable endogenous small interfering RNAs (endo-siRNAs) revealed that the SET-25-dependent heritable endo-siRNAs target newly acquired and highly H3K9me3 marked genes. Thus, \"repressive\" chromatin marks could be important specifically for heritable silencing of genes which are flagged as \"foreign\", such as gfp.

Source connections

Explore related subjects

geneticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lev, I., Gingold, H., Rechavi, O.. 2018-06-04. H3K9me3 is Required for Transgenerational Inheritance of Small RNAs that Target a Unique Subset of Newly Evolved Genes. https://doi.org/10.1101/338582

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Mapping, stacking and characterization of a novel resistance haplotype against GpaVvrn-virulent Globodera pallida derived from wild potato relative Solanum brevicaule

Potato production is threatened by pests and pathogens. Among the most harmful are the potato cyst nematodes (PCN), including Globodera pallida. The major control measures are potato cultivars harbouring resistance genes. However, virulent nematode populations are breaking through the most broadly applied resistance genes, and therefore novel resistance genes are required to keep control of G. pallida. In this study we map a resistance locus in wild potato relative Solanum brevicaule to the bottom of chromosome 11 (42.83 - 42.85 Mb) using a k-mer based bulked segregant analysis and name the resistant haplotype GpaXIbrc. The presence of the GpaXIbrc marker in the potato genome significantly increases resistance against a GpaVvrn-virulent G. pallida population (AMPOP01). Furthermore, the GpaXIbrc haplotype was stacked with three other resistance haplotypes: GpaXItar, GpaVvrn, and GpaIXvrn. Stacking of the novel GpaXIbrc haplotype to these other resistance haplotypes resulted in a significant increase in resistance. The largest effect was seen in combinations with 'major' resistance haplotypes GpaVvrn + GpaIXvrn and GpaXItar + GpaXIbrc. To determine whether we are dealing with a novel allele, the resistance mechanism underlying the GpaXIbrc haplotype was described after performing an in vitro bioassay. The resistance mechanism was different from GpaXIspl as described in literature, which is also localized at the bottom of chromosome 11. Therefore, we conclude that we found a novel resistance allele originating from S. brevicaule.

genetics↗
bioRxiv2026

Cellular context shapes the transcriptomic impact of somatic variants

Somatic SNVs are commonly prioritized by recurrence or sequence annotation, leaving the molecular consequences of private variants unresolved. We developed PrismSNV and Ligo-Seq, a single-cell full-length transcriptome sequencing platform, to quantify transcriptomic displacement associated with within-cell SNV-state toggling. Across 26 samples from three cancer types, more than 60% of candidate SNVs showed significant cell-type-specific displacement with over 30% variation in magnitude. Sequence-based deleteriousness was poorly aligned with cellular displacement, and fewer than 3% of top-displacement SNVs across six tumor types were catalogued in ClinVar. Displacement was strongest in transcriptionally plastic, less differentiated states. Analysis of 655,349 CD4+ T-cell transcriptomes further showed that SNV-gene associations changed in magnitude and sometimes direction during activation. Lack of recurrence or clinical annotation does not imply transcriptomic inertness; variant impact is shaped by cellular context rather than sequence alone, establishing the variant-cell pair as a critical unit for interpreting somatic variation.

genetics↗
bioRxiv2026

Genetic and Epigenetic Landscape of Self-Identified Hispanics/Latino in All Of Us

Human genetic studies still underrepresent many populations, limiting discovery and interpretation of medically relevant variation. Extensive admixture in self-identified Hispanic/Latino populations increases the need for representative reference data and ancestry-aware interpretation of medically relevant variation. We used long-read sequencing to analyze genetic variation, ancestry, and DNA methylation in 1,490 self-identified Hispanic/Latino participants from the All of Us Research Program. We identified 10 million novel variants and more than 100 candidate phenotype associations, with fine-mapping prioritizing structural variants over nearby single-nucleotide variants in more than half. We linked 3,329 tandem repeats to DNA methylation, resolved widespread allele-specific methylation, and identified ancestry-linked regulation across paralogous genes. These results reveal previously inaccessible genetic and regulatory variation and show the value of long-read sequencing for diverse populations.

genetics↗