Gametes deficient for Pot1 telomere binding proteins alter levels of telomeric foci for multiple generations

Evan H Lister-Shimauchi,Shawn Ahmed,Michael Dinh,Paul Maddox

doi:10.1038/s42003-020-01624-7

Evan H Lister-Shimauchi, Shawn Ahmed + Show 2 more

Open Access

https://doi.org/10.1038/s42003-020-01624-7

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Abstract

Deficiency for telomerase results in transgenerational shortening of telomeres. However, telomeres have no known role in transgenerational epigenetic inheritance. C. elegans Protection Of Telomeres 1 (Pot1) proteins form foci at the telomeres of germ cells that disappear at fertilization and gradually accumulate during development. We find that gametes from mutants deficient for Pot1 proteins alter levels of telomeric foci for multiple generations. Gametes from pot-2 mutants give rise to progeny with abundant POT-1::mCherry and mNeonGreen::POT-2 foci throughout development, which persists for six generations. In contrast, gametes from pot-1 mutants or pot-1; pot-2 double mutants induce diminished Pot1 foci for several generations. Deficiency for MET-2, SET-25, or SET-32 methyltransferases, which promote heterochromatin formation, results in gametes that induce diminished Pot1 foci for several generations. We propose that C. elegans POT-1 may interact with H3K9 methyltransferases during pot-2 mutant gametogenesis to induce a persistent form of transgenerational epigenetic inheritance that causes constitutively high levels of heterochromatic Pot1 foci.

Highlights

Deficiency for telomerase results in transgenerational shortening of telomeres
We find that gametes from mutants that lack C. elegans POT-1 or POT-2 single-stranded telomere binding proteins induce altered levels of telomeric foci for multiple generations
Wild-type POT-1 protein must be present in both parents in order for their gametes to create progeny with stable Pot[1] foci

Summary

Introduction

Deficiency for telomerase results in transgenerational shortening of telomeres. telomeres have no known role in transgenerational epigenetic inheritance. We find that gametes from mutants deficient for Pot[1] proteins alter levels of telomeric foci for multiple generations. Deficiency for MET-2, SET-25, or SET-32 methyltransferases, which promote heterochromatin formation, results in gametes that induce diminished Pot[1] foci for several generations. We propose that C. elegans POT-1 may interact with H3K9 methyltransferases during pot-2 mutant gametogenesis to induce a persistent form of transgenerational epigenetic inheritance that causes constitutively high levels of heterochromatic Pot[1] foci. Mammalian POT1 is part of a six subunit protein complex, termed shelterin, which interacts with telomeres to promote telomere stability and prevent chromosome termini from being recognized as DNA damage[10,11]. Aside from 3′ single-stranded telomeric overhangs that are created in the context of telomere replication, POT1 may interact with single-stranded telomeric

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