The SET-2/SET1 Histone H3K4 Methyltransferase Maintains Pluripotency in the Caenorhabditis elegans Germline

Histone H3 Lys 4 methylation (H3K4me) is deposited by the conserved SET1/MLL methyltransferases acting in multiprotein complexes, including Ash2 and Wdr5. Although individual subunits contribute to complex activity, how they influence gene expression in specific tissues remains largely unknown. In Caenorhabditis elegans, SET-2/SET1, WDR-5.1, and ASH-2 are differentially required for germline H3K4 methylation. Using expression profiling on germlines from animals lacking set-2, ash-2, or wdr-5.1, we show that these subunits play unique as well as redundant functions in order to promote expression of germline genes and repress somatic genes. Furthermore, we show that in set-2- and wdr-5.1-deficient germlines, somatic gene misexpression is associated with conversion of germ cells into somatic cells and that nuclear RNAi acts in parallel with SET-2 and WDR-5.1 to maintain germline identity. These findings uncover a unique role for SET-2 and WDR-5.1 in preserving germline pluripotency and underline the complexity of the cellular network regulating this process. [Display omitted] •H3K4 methylation represses expression of somatic genes in the C. elegans germline•Loss of H3K4 methylation results in germline transdifferentiation•Transdifferentiation increases across generations•The nuclear RNAi pathway contributes to the maintenance of germ cell identity Germ cells are totipotent, meaning that they can give rise to all cells of an organism. Robert et al. identify a function for H3K4 methylation, a histone modification mediated by the SET-2/SET1 methyltransferase, in repressing somatic gene expression in the C. elegans germline. In the absence of SET-2/SET1 and H3K4 methylation, germ cells differentiate into somatic cells, indicating that H3K4 methylation helps preserve germ cell identity.