Organ transformation by environmental disruption of epigenetic memory

Abstract

AbstractUnlike recent progress in cellular reprogramming, the mechanisms and requirements for misspecification of entire organs are largely unknown. A canonic model for organ “reprogramming” was provided by the induction of haltere-to-wing transformations in response to early exposure of fly embryos to ether. Using this model, we identify a mechanistic chain of events explaining why and how stage-specific exposure leads to organ transformation at a later stage. We show that ether interferes with protein integrity and compromises Trithorax-mediated establishment of H3K4 tri-methylations. The altered pattern of H3K4me3 pre-disposes early-methylated Ubx targets and wing genes for later up-regulation in the larval haltere disc, hence the wing-like outcome. Consistent with protein destabilization by ether, this transformation is enhanced by reduced function of Hsp90 and emerges spontaneously by joint deficiency in Hsp90 and Trithorax. The morphogenetic impact of chaperone response at the onset of epigenetic patterning may comprise a general scheme for organ reprogramming by environmental cues.