Early embryonic heat shock induces long-term epigenetic memory by affecting the transition to zygotic independence

Early-life stress can generate persistent life-long effects that impact adult health and disease risk, but little is known of how such programming is established and maintained. Previous use of the Drosophila strain wm4h show that an early embryonic heat shock result in stable epigenetic alteration in the adult fly. To investigate the potential role of small non-coding RNA (sncRNA) in the initiation of such long-term epigenetic effects, we here generated a fine timeline of sncRNA expression during the first 5 stages of Drosophila embryogenesis in this strain. Building on this, we show that (1) miRNA is increased following early embryonic heat shock, and (2) the increased miRNA is coming from two separate sources, maternal and zygotic. By performing long RNA sequencing on the same single embryo, we found that a subgroup of miRNA with maternal origin, had a strong negative correlation with a group of early zygotic transcripts. Critically, we found evidence that one such early zygotic transcript, the insulator binding factor Elba1, is a Su(var) for wm4h. The findings provide insights of the dynamics and stress-sensitivity of sncRNA during the first embryonic stages in Drosophila and suggest an interplay between miRNA, Elba1 and long-term epigenetic alteration. HIGHLIGHTSO_LIWe provide a high-resolution timeline for sncRNA for Drosophila stage 1-5 embryos C_LIO_LIHeat shock before midblastula transition (MBT) results in a massive upregulation of miRNA at cellularization C_LIO_LIHeat shock-induced miRNAs negatively associate with downregulation of a specific subset of pre-MBT genes C_LIO_LIElba1 is a position-effect-variegation (PEV) modifier for wm4h C_LIO_LIHeat shock-induces an "leaky" expression of genes that overlap with Elba 1-3 binding sites C_LI