title: SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state during passage through the germ line.
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.
authors: School of Biology, Georgia Institute of Technology, Atlanta, GA 30332;Fellowships in Research and Science Teaching and.
authors: Shana C
authors: SC
authors: Kerr
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322;Graduate Division of Biological and Biomedical Science, Emory University, Atlanta, GA 30322; and.
authors: Chelsey Chandler
authors: CC
authors: Ruppersburg
authors: Graduate Division of Biological and Biomedical Science, Emory University, Atlanta, GA 30322; andDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.
authors: Joshua W
authors: JW
authors: Francis
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322; djkatz@emory.edu.
authors: David J
authors: DJ
authors: Katz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D005854:Germ Cells / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D040582:Inheritance Patterns / Q000235:genetics*; D008857:Microscopy, Interference; D008957:Models, Genetic; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D006657:Histones; D010089:Oxidoreductases, N-Demethylating; C468848:SPR-5 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase; C523531:Met-2 protein, C elegans