Poulin, Gino et al. (2021) International Worm Meeting "RBBP-5 regulated methylation at Histone 3 Lysine 4 promotes longevity in C. elegans"

Vintilla, Adriana, Fisher, Kate, Whitmarsh, Alan, Samsudin, Nurulhafizah, Fei, Pang Yoke, Velichkova, Gabriel, Poulin, Gino

[International Worm Meeting, 2021]

Histone 3 lysine 4 methylation (H3K4me) is an epigenetic mark regulating transcription, metabolism, and longevity. H3K4me necessitates, in addition to KMT2 enzymes, the conserved core components WDR5, ASH2, and RBBP5. In C. elegans, deficiency in WDR-5 or ASH-2 reduces H3K4me3 levels and extends lifespan. Transgenerational experiments whereby only the parental generation is deficient in WDR-5 or ASH-2 leads to incomplete reprogramming of the next generation resulting in long-lived descendants. Whether RBBP-5 has similar functions remains unclear. Herein, using spike in ChIP-seq, we show that RBBP-5 is required for H3K4 mono- and multi-methylation and adults lacking RBBP-5 are short-lived. In contrast with WDR-5 or ASH-2 deficiencies, our transgenerational experiments show that reprogramming of the next wild type generation is normal. Instead, we revealed that RBBP-5-deprived descendants originating from mothers heterozygous for the rbbp-5 deficiency inherit a wild type lifespan. However, at the fifth generation the rbbp-5(-) short-lived phenotype fully manifest. Using RNA-seq and reporter assays, we found that RBBP-5 is important to maintain mitochondrial bioenergetic and core translational functions. We also show that restoring RBBP-5 expression in the soma is sufficient to recapitulate the wild type lifespan, hence ruling out the germlines as the primary site for H3K4me longevity promoting functions. Collectively, this work shows RBBP-5 regulated H3K4me promotes longevity and wild type lifespan can be epigenetically transmitted to H3K4me-depleted descendants most likely by a mechanism alleviating mitochondrial and translational dysfunctions in somatic cells.

Florence Couteau et al. (2003) International Worm Meeting "Nuclear reorganization, homologue pairing, and normal completion of recombination require a component of the meiotic chromosome core"

Florence Couteau, Monique Zetka, Kentaro Nabeshima, Anne Villeneuve

[International Worm Meeting, 2003]

Meiotic chromosomes undergo complex structural changes whose relationship to conserved processes like recombination, homologue pairing, and synapsis are poorly understood. Following DNA replication, a proteinaceous axis known as a chromosome core forms between sister chromatids. Once homologously paired, the cores are anchored by the synaptonemal complex. We have previously characterized the him-3 gene, which encodes a chromosome core component required for synapsis and recombination (Zetka et al. 1999). Recently, we have characterized new alleles of him-3 - the deletion null allele gk149 and the missense mutations me80 and vv6 that have demonstrated previously unknown roles for the protein in nuclear reorganization, homologue recognition, and the normal completion of recombination events. The germ lines of gk149 animals lack the polarized nuclei typical of early prophase, indicating that HIM-3 is required for the spatial reorganization of the nucleus. All three mutants show severe defects in homologue recognition and synapsis, indicating that HIM-3 is required for both synapsis-independent pairing and for the assembly of the SC. Surprisingly, recombination appears to be initiated at wild-type levels in all three mutants as evidenced by staining with anti-RAD-51, indicating that recombination initiation and early homologue alignment are independent processes. These foci, however, persist and accumulate in vv6 and me80 homozygotes and a significant increase in the number of germ cell corpses is observed, suggesting that the pachytene DNA damage checkpoint was triggered. The RAD-51 foci of gk149 animals, however, showed wild-type kinetics of disappearance and no increase in germ cell apoptosis was observed. These observations can be interpreted in light of an important feature of normal meiotic recombination, that recombination events are directed to occur preferentially between chromatids of homologous chromosomes rather than between sister chromatids. We hypothesize that recombination intermediates persist in the non-null him-3 mutants because the barriers that inhibit utilization of sister chromatids as repair partners persist in the presence of the him-3 mutant proteins; in the absence of HIM-3, this inhibition is alleviated and initiated events can be efficiently repaired by sister chromatid recombination. The authors are grateful to Dr. Adriana LaVolpe for providing the anti-RAD51 antisera. This work was supported by an NSERC (Canada) grant to M.Z. and an NIH (USA) grant to A.V.