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

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. © 2011 li,kelly.