SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state during passage through the germ line

• Type of Material: Article
• Authors: Shana C. Kerr, Georgia Institute of Technology; Chelsey Chandler Ruppersburg, Emory University; Joshua W. Francis, Emory University; David Katz, Emory University
• Language: English
• Date: 2014-07-01
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: 2014 National Academy of Sciences
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1321843111
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• Volume: 111
• Issue: 26
• Start Page: 9509
• End Page: 9514
• Grant/Funding Information: S.C.K. was supported by the Fellowships in Research and Science Teaching postdoctoral fellowship program.; C.C.R. was supported by a Biochemistry, Cell and Molecular Biology Training Grant (5T32GM008367).
• Keywords: MEMORY; Multidisciplinary Sciences; Science & Technology - Other Topics; Science & Technology; METHYLTRANSFERASE; HISTONE H3; METHYLATION; NUCLEAR TRANSFER; CAENORHABDITIS-ELEGANS; C. ELEGANS; VULVAL DEVELOPMENT; TRANSCRIPTION; HETEROCHROMATIN FORMATION
• Research Categories: Biology, Cell; Chemistry, Biochemistry

Abstract

The Caenorhabditis elegans LSD1 H3K4me2 demethylase SPR-5 reprograms epigenetic transcriptional memory during passage through the germ line. Here we show that mutants in the H3K9me2 methyltransferase, met-2, result in transgenerational epigenetic effects that parallel spr-5 mutants. In addition, we find that spr-5;met-2 double mutants have a synergistic effect on sterility, H3K4me2, and spermatogenesis expression. These results implicate MET-2 as a second histone-modifying enzyme in germ-line reprogramming and suggest a model in which SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state required for the continued immortality of the C. elegans germ line.Without SPR-5 and MET-2,we find that the ability to express spermatogenesis genes is transgenerationally passed on to the somatic cells of the subsequent generation. This indicates that H3K4me2 may act in the maintenance of cell fate. Finally, we demonstrate that reducing H3K4me2 causes a large increase in H3K9me2 added by the SPR-5;MET-2 reprogramming mechanism. This finding suggests a novel histone code interaction in which the input chromatin environment dictates the output chromatin state. Taken together, our results provide evidence for a broader reprogramming mechanism in which multiple enzymes coordinately regulate histone information during passage through the germ line.