Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation inC. elegansembryos

ONE SENTENCE SUMMARY MET-2/SETDB1 and interactors (LIN-65/ATF7IP and ARLE-14/ARL14EP) initiate heterochromatin formation during embryogenesis. ABSTRACT Heterochromatin formation during early embryogenesis is timed precisely, but it has been elusive how this process is regulated. Here we report the discovery of a histone methyltransferase complex whose nuclear accumulation determines the onset of heterochromatin formation in C. elegans embryos. We find that the inception of heterochromatin generation coincides with the nuclear accumulation of the methyltransferase MET-2 (SETDB). The absence of MET-2 results in delayed and disturbed heterochromatin formation, whereas accelerated nuclear localization of the methyltransferase leads to precocious heterochromatin. We identify two factors that bind to and function with MET-2: LIN-65, which resembles ATF7IP, localizes MET-2 into nuclear hubs, and ARLE-14, orthologous to ARL14EP, promotes stable association of MET-2 with chromatin. These data reveal that nuclear accumulation of MET-2 in conjunction with LIN-65 and ARLE-14 regulates timing of heterochromatin domains during embryogenesis.