A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line

• Published in: PLoS genetics Vol. 7; no. 3; p. e1001349
• Main Authors: Li, Tengguo, Kelly, William G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2011; Public Library of Science (PLoS)
• Subjects: Animals; Biomedical research; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell cycle; Developmental Biology/Embryology; Developmental Biology/Germ Cells; Developmental Biology/Stem Cells; Epigenetics; Epigenomics; Experiments; Gene expression; Gene Expression Regulation, Developmental; Genetic aspects; Genetics; Genetics and Genomics/Chromosome Biology; Genetics and Genomics/Epigenetics; Genome, Helminth - genetics; Germ Cells - metabolism; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Histones; Histones - metabolism; Methylation; Methyltransferases - genetics; Methyltransferases - metabolism; Myeloid-Lymphoid Leukemia Protein - metabolism; Nuclear Proteins - metabolism; Physiological aspects; RNA Interference; RNA polymerase; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Stem cells; Transcription, Genetic; Yeast; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1001349

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.