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

Lev, Itamar; Gingold, Hila; Rechavi, Oded

doi:10.1101/338582

Cited by 11 publications

(11 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that hrde-1, nrde-3 and rrf-1 mutants, as well as additional mutants defective in siRNA biogenesis (rde-1, rde-4, rrf-3 and mut-16), are not required for the inheritance of the elongated morphology (figure 4). Previously, histone-H3-lysine-9 (H3K9) methylations were implicated in trans-generational inheritance of small RNAs [47][48][49][50]. H3K9 mono-and di-methylations are deposited by the MET-2 methyltransferase [51], while H3K9me3 is deposited by the SET-25 and SET-32 methyltransferases [51,52].…”

Section: (D) Progeny Of Liquid-grown Worms Are Longer Even In Mutantsmentioning

confidence: 99%

Inter-generational consequences for growing Caenorhabditis elegans in liquid

Lev

Bril

Liu

et al. 2019

Phil. Trans. R. Soc. B

Self Cite

View full text Add to dashboard Cite

In recent years, studies in Caenorhabditis elegans nematodes have shown that different stresses can generate multigenerational changes. Here, we show that worms that grow in liquid media, and also their plate-grown progeny, are different from worms whose ancestors were grown on plates. It has been suggested that C. elegans might encounter liquid environments in nature, although actual observations in the wild are few and far between. By contrast, in the laboratory, growing worms in liquid is commonplace, and often used as an alternative to growing worms on agar plates, to control the composition of the worms' diet, to starve (and synchronize) worms or to grow large populations for biochemical assays. We found that plate-grown descendants of M9 liquid medium-grown worms were longer than control worms, and the heritable effects were already apparent very early in development. We tested for the involvement of different known epigenetic inheritance mechanisms, but could not find a single mutant in which these inter-generational effects are cancelled. While we found that growing in liquid always leads to inter-generational changes in the worms’ size, trans-generational effects were found to be variable, and in some cases, the effects were gone after one to two generations. These results demonstrate that standard cultivation conditions in early life can dramatically change the worms' physiology in adulthood, and can also affect the next generations. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

show abstract

Section: (D) Progeny Of Liquid-grown Worms Are Longer Even In Mutantsmentioning

confidence: 99%

Inter-generational consequences for growing Caenorhabditis elegans in liquid

Lev

Bril

Liu

et al. 2019

Phil. Trans. R. Soc. B

Self Cite

View full text Add to dashboard Cite

show abstract

“…Typically, dsRNA-triggered heritable responses persist for 3-5 generations 6,7 , owing to a dedicated pathway which regulates the duration of each heritable response 7,8 . Maintenance of RNAi interference (RNAi) over generations involves specialized argonaute proteins [9][10][11] , amplification of the small RNAs by RNA-dependent RNA Polymerases 12,13 (RdRPs), and chromatin modifiers 8,[14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Germ Granules Functions are Memorized by Transgenerationally Inherited Small RNAs

Lev

Toker

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules (pptr-1, meg-3/4, pgl-1) can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity. Animals mutated in pptr-1, which is required for stabilization of P granules in the early embryo, display extremely strong heritable RNAi responses, which last for tens of generations, long after the responses in wild type animals peter out. The phenotype of mutants defective in the core germ granules proteins MEG-3 and MEG-4, depends on the genotype of the ancestors: Mutants that derive from maternal lineages that had functional MEG-3 and MEG-4 proteins exhibit enhanced RNAi inheritance for multiple generations. While functional ancestral meg-3/4 alleles correct, and even potentiates the ability of mutant descendants to inherit RNAi, defects in germ granules functions can be memorized as well; Wild type descendants that derive from lineages of mutants show impaired RNAi inheritance for many (>16) generations, although their germ granules are intact. Importantly, while P granules are maternally deposited, wild type progeny derived from meg-3/4 male mutants also show reduced RNAi inheritance. Unlike germ granules, small RNAs are inherited also from the sperm.Moreover, we find that the transgenerational effects that depend on the ancestral germ granules require the argonaute protein HRDE-1, which carries heritable small RNAs in the germline. Indeed, small RNA sequencing reveals imbalanced levels of many endogenous small RNAs in germ granules mutants. Strikingly, we find that hrde-1;meg-3/4 triple mutants inherit RNAi, although hrde-1 was previously thought to be essential for heritable silencing. We propose that germ granules sort and shape the RNA pool, and that small RNA inheritance memorizes this activity for multiple generations.

show abstract

“…How small RNAs cooperate with repressive histone PTMs in epi genetic inheritance is currently unclear 44,46,48,50 . Although the inactivation of RNAi components such as HRDE1 or NRDE2 did not affect the transmission of this H3K9me3mediated epigenetic memory 54 , very recent data argue that H3K9me3 might be required for siRNA dependent TEI that specifically targets newly evolved genes and is particularly sensitive to transgenes 55 .…”

Section: Histone Ptm Inheritance In Caenorhabditis Elegansmentioning

confidence: 98%

Functions and mechanisms of epigenetic inheritance in animals

Skvortsova

Iovino

Bogdanović

2018

Nat Rev Mol Cell Biol

376

259

View full text Add to dashboard Cite

| The idea that epigenetic determinants such as DNA methylation, histone modifications or RNA can be passed to the next generation through meiotic products (gametes) is long standing. Such meiotic epigenetic inheritance (MEI) is fairly common in yeast, plants and nematodes, but its extent in mammals has been much debated. Advances in genomics techniques are now driving the profiling of germline and zygotic epigenomes, thereby improving our understanding of MEI in diverse species. Whereas the role of DNA methylation in MEI remains unclear, insights from genome-wide studies suggest that a previously underappreciated fraction of mammalian genomes bypass epigenetic reprogramming during development. Notably , intergenerational inheritance of histone modifications, tRNA fragments and microRNAs can affect gene regulation in the offspring. It is important to note that MEI in mammals rarely constitutes transgenerational epigenetic inheritance (TEI), which spans multiple generations. In this Review , we discuss the examples of MEI in mammals, including mammalian epigenome reprogramming, and the molecular mechanisms of MEI in vertebrates in general. We also discuss the implications of the inheritance of histone modifications and small RNA for embryogenesis in metazoans, with a particular focus on insights gained from genome-wide studies.

show abstract

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

Cited by 11 publications

References 56 publications

Inter-generational consequences for growing Caenorhabditis elegans in liquid

Inter-generational consequences for growing Caenorhabditis elegans in liquid

Germ Granules Functions are Memorized by Transgenerationally Inherited Small RNAs

Functions and mechanisms of epigenetic inheritance in animals

Contact Info

Product

Resources

About