title: A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line.
abstract: The methylation of lysine 4 of Histone H3 (H3K4me) is an important component of epigenetic regulation. H3K4 methylation is a consequence of transcriptional activity, but also has been shown to contribute to "epigenetic memory"; i.e., it can provide a heritable landmark of previous transcriptional activity that may help promote or maintain such activity in subsequent cell descendants or lineages. A number of multi-protein complexes that control the addition of H3K4me have been described in several organisms. These Set1/MLL or COMPASS complexes often share a common subset of conserved proteins, with other components potentially contributing to tissue-specific or developmental regulation of the methyltransferase activity. Here we show that the normal maintenance of H3K4 di- and tri-methylation in the germ line of Caenorhabditis elegans is dependent on homologs of the Set1/MLL complex components WDR-5.1 and RBBP-5. Different methylation states that are each dependent on wdr-5.1 and rbbp-5 require different methyltransferases. In addition, different subsets of conserved Set1/MLL-like complex components appear to be required for H3K4 methylation in germ cells and somatic lineages at different developmental stages. In adult germ cells, mutations in wdr-5.1 or rbbp-5 dramatically affect both germ line stem cell (GSC) population size and proper germ cell development. RNAi knockdown of RNA Polymerase II does not significantly affect the wdr-5.1-dependent maintenance of H3K4 methylation in either early embryos or adult GSCs, suggesting that the mechanism is not obligately coupled to transcription in these cells. A separate, wdr-5.1-independent mode of H3K4 methylation correlates more directly with transcription in the adult germ line and in embryos. Our results indicate that H3K4 methylation in the germline is regulated by a combination of Set1/MLL component-dependent and -independent modes of epigenetic establishment and maintenance.
authors: Biology Department, Rollins Research Center, Emory University, Atlanta, Georgia, United States of America.
authors: Tengguo
authors: T
authors: Li
authors: William G
authors: WG
authors: Kelly
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D057890:Epigenomics; D018507:Gene Expression Regulation, Developmental; D049751:Genome, Helminth / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D034622:RNA Interference; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D009687:Nuclear Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C464501:Set-1 protein, C elegans; D012319:RNA Polymerase II