Gene expression is profoundly influenced by histone methylation: marks such as H3K4me and H3K36me are associated with active transcription, whereas repressive marks such as H3K9me are associated with transcriptional repression. In Caenorhabditis elegans, the maternally provided demethylase SPR-5 and methyltransferase MET-2 play key roles in reprogramming the zygote, whereas the methyltransferase MES-4 maintains methylation in a subset of germline genes in the early embryo. Brandon Carpenter, David Katz and colleagues now address how inherited histone methylation regulates developmental gene expression in worms. They first show that spr-5; met-2 mutants have a severe developmental delay. Genomic analysis of these mutants reveals a significant upregulation of genes normally expressed in the germline, and a significant overlap between the upregulated genes and genes previously known to be bound by MES-4. smFISH confirms ectopic somatic upregulation for two targets, htp-1 and cpb-1; ectopic H3K36me3 is also seen to be maintained in MES-4 germline genes. Strikingly, knockdown of MES-4 rescues both the aberrant somatic expression of germline genes and developmental delay of the mutants. In addition, developmental delay is rescued by knockdown of SET-2 and, finally, the authors find that somatic tissues in the mutants acquire the ability to silence transgenes, which usually only happens in the germline. Proper inheritance of histone methylation is thus crucial both to establish the soma/germline barrier and for timely progression through development.
