PXD050958

PXD050958 is an original dataset announced via ProteomeXchange.

Title	Waddington revisited: Organ transformation by environmental disruption of protein integrity and epigenetic memory in Drosophila
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-04-24
AnnouncementXML	Submission_2024-04-24_09:37:07.687.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yulia Gnainsky
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-25 09:14:05	ID requested
⏵ 1	2024-04-24 09:37:08	announced

Dataset with its publication pending

submitter keyword: Bithorax phenocopy, chaperone response, epigenetic memory, Ubx, fly embryos, haltere-to-wing transformation, heat-shock proteins, haltere, diethyl ether, protein-misfolding, Trithorax, Waddington, Ultrabithorax, wing, epigenetics, Trx, development, organogenesis, Hsp90, H3K27 tri-methylation, H3K4 tri-methylation

Yoav Soen
contact affiliation	Department of the Biomolecular Sciences, Weizmann Institute of Science, Israel
contact email	yoavs@weizmann.ac.il
lab head
Yulia Gnainsky
contact affiliation	Weizmann Institute of science
contact email	yulia.gnainsky@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050958
     1. Label: PRIDE project
     2. Name: Waddington revisited: Organ transformation by environmental disruption of protein integrity and epigenetic memory in Drosophila