Chromatin Modifiers SET-25 and SET-32 Are Required for Establishment but Not Long-Term Maintenance of Transgenerational Epigenetic Inheritance

Rachel M Woodhouse; Gabriele Buchmann; Matthew Hoe; Dylan J Harney; Jason K K Low; Mark Larance; Peter R Boag; Alyson Ashe

doi:10.1016/j.celrep.2018.10.085

Chromatin Modifiers SET-25 and SET-32 Are Required for Establishment but Not Long-Term Maintenance of Transgenerational Epigenetic Inheritance

Cell Rep. 2018 Nov 20;25(8):2259-2272.e5. doi: 10.1016/j.celrep.2018.10.085.

Authors

Rachel M Woodhouse¹, Gabriele Buchmann¹, Matthew Hoe¹, Dylan J Harney², Jason K K Low¹, Mark Larance², Peter R Boag³, Alyson Ashe⁴

Affiliations

¹ The University of Sydney, School of Life and Environmental Sciences, Sydney, NSW 2006, Australia.
² The University of Sydney, Charles Perkins Centre, School of Life and Environmental Sciences, Sydney, NSW 2006, Australia.
³ Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Clayton, VIC 3800, Australia.
⁴ The University of Sydney, School of Life and Environmental Sciences, Sydney, NSW 2006, Australia; The University of Wollongong, School of Biological Sciences and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. Electronic address: alyson.ashe@sydney.edu.au.

PMID: 30463020
DOI: 10.1016/j.celrep.2018.10.085

Abstract

Some epigenetic modifications are inherited from one generation to the next, providing a potential mechanism for the inheritance of environmentally acquired traits. Transgenerational inheritance of RNAi phenotypes in Caenorhabditis elegans provides an excellent model to study this phenomenon, and although studies have implicated both chromatin modifications and small RNA pathways in heritable silencing, their relative contributions remain unclear. Here, we demonstrate that the putative histone methyltransferases SET-25 and SET-32 are required for establishment of a transgenerational silencing signal but not for long-term maintenance of this signal between subsequent generations, suggesting that transgenerational epigenetic inheritance is a multi-step process with distinct genetic requirements for establishment and maintenance of heritable silencing. Furthermore, small RNA sequencing reveals that the abundance of secondary siRNAs (thought to be the effector molecules of heritable silencing) does not correlate with silencing phenotypes. Together, our results suggest that the current mechanistic models of epigenetic inheritance are incomplete.

Keywords: RNAi; chromatin; epigenetics; inheritance; small RNA; transgenerational.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caenorhabditis elegans / embryology
Caenorhabditis elegans / genetics*
Caenorhabditis elegans Proteins / metabolism*
Chromatin / metabolism*
Epigenesis, Genetic*
Gene Silencing
Germ Cells / metabolism
Histone Methyltransferases / metabolism*
Histone-Lysine N-Methyltransferase / metabolism*
Histones / metabolism
Inheritance Patterns / genetics*
Longevity
Lysine / metabolism
Male
Methylation
Models, Genetic
Mutation / genetics
Phenotype
RNA / metabolism
RNA, Small Interfering / metabolism
Spermatozoa / metabolism

Substances

Caenorhabditis elegans Proteins
Chromatin
Histones
RNA, Small Interfering
RNA
Histone Methyltransferases
set-32 protein, C elegans
Histone-Lysine N-Methyltransferase
SET-25 protein, C elegans
Lysine

Grants and funding

P40 OD010440/OD/NIH HHS/United States