Waddington revisited: Organ transformation by environmental disruption of protein integrity and epigenetic memory in Drosophila

ABSTRACT: Despite significant progress in the mechanistic understanding of epigenetic reprogramming of cells, the basis of 'organ reprogramming' by (epi-)gene-environment interactions remained largely obscured. Here, we use the ether-induced haltere-to-wing transformations in Drosophila as a model for epigenetic “reprogramming� at the whole organism level. Our findings support a mechanistic chain of events explaining why and how brief embryonic exposure to ether leads to organ transformation manifested at the larval stage and on. We show that ether interferes with protein integrity in the egg leading to altered deployment of Hsp90 and widespread repression of Trithorax-mediated establishment of H3K4 tri-methylations throughout the genome. Despite this global suppression of H3K4me3, Ubx targets, and wing development genes preferentially retain higher levels of active chromatin marks. This preferential retention pre-disposes Ubx targets and wing genes for later up-regulation in the larval haltere disc, hence the wing-like outcome. Consistent with compromised protein integrity during the exposure, the penetrance of bithorax transformation increases by genetic or chemical reduction of Hsp90 function. Moreover, joint reduction in Hsp90 and trx gene dosage can cause bithorax transformations even without exposure to ether, supporting underlying epistasis between Hsp90 and trx loss-of-functions. These findings implicate environmental disruption of protein integrity at the onset of histone methylations with a modification of epigenetic memory. The emerging picture provides a unique example in which the alleviation of the Hsp90 ‘capacitor function’ by the environment leads to a morphogenetic shift towards an ancestral-like body plan. The morphogenetic impact of chaperone response during a major setup of epigenetic patterns may be a general scheme for organ reprogramming by environmental cues.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Embryo

SUBMITTER: Yulia Gnainsky  

LAB HEAD: Yoav Soen

PROVIDER: PXD050958 | Pride | 2024-04-24

REPOSITORIES: Pride