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Örkenby L, Skog S, Ekman H, Gozzo A, Kugelberg U, Ramesh R, Magadi S, Zambanini G, Nordin A, Cantú C, Nätt D, Öst A
Mol. Syst. Biol. 19 (5) e11148 [2023-05-09; online 2023-03-20]
Early-life stress can result in life-long effects that impact adult health and disease risk, but little is known about how such programming is established and maintained. Here, we show that such epigenetic memories can be initiated in the Drosophila embryo before the major wave of zygotic transcription, and higher-order chromatin structures are established. An early short heat shock results in elevated levels of maternal miRNA and reduced levels of a subgroup of zygotic genes in stage 5 embryos. Using a Dicer-1 mutant, we show that the stress-induced decrease in one of these genes, the insulator-binding factor Elba1, is dependent on functional miRNA biogenesis. Reduction in Elba1 correlates with the upregulation of early developmental genes and promotes a sustained weakening of heterochromatin in the adult fly as indicated by an increased expression of the PEV wm4h reporter. We propose that maternal miRNAs, retained in response to an early embryonic heat shock, shape the subsequent de novo heterochromatin establishment that occurs during early development via direct or indirect regulation of some of the earliest expressed genes, including Elba1.
Clinical Genomics Linköping [Service]
PubMed 36938679
DOI 10.15252/msb.202211148
Crossref 10.15252/msb.202211148