PXD036038-1

PXD036038 is an original dataset announced via ProteomeXchange.

Title	Interactome of the long non-protein coding RNA (lncRNA) D4Z4 binding element-transcript (DBE-T)
Description	Facioscapulohumeral muscular dystrophy (FSHD) is an inherited progressive neuromuscular disorder that afflicts both children and adults regardless of gender. FSHD is caused by aberrant gain of expression of the transcription factor DUX4, which triggers a pro-apoptotic transcriptional program leading to muscle wasting. As today, no cure or therapeutic option is available to FSHD patients. Given its centrality in FSHD, blocking DUX4 expression with small molecule drugs is an attractive option. We previously showed that the long non-coding RNA DBE-T is required for aberrant DUX4 expression in FSHD. Using affinity purification followed by proteomics, we identified the chromatin remodeling protein WDR5 as a novel DBE-T interactor and a key player required for the biological activity of the lncRNA. We found that WDR5 is required for the expression of DUX4 and its targets in primary FSHD muscle cells. Moreover, targeting WDR5 rescues both cell viability and myogenic differentiation of FSHD patient cells. Notably, comparable results were obtained by pharmacological inhibition of WDR5. Importantly, WDR5 targeting was safe to healthy donor muscle cells. Our results support a pivotal role of WDR5 in the activation of DUX4 expression identifying a druggable target for an innovative therapeutic approach for FSHD.
HostingRepository	PRIDE
AnnounceDate	2023-04-11
AnnouncementXML	Submission_2023-04-11_08:37:34.549.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036038
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	AnnapaolaAndolfo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-12 13:38:18	ID requested
⏵ 1	2023-04-11 08:37:34	announced

10.6019/PXD036038;

submitter keyword: facioscapulohumeral muscular dystrophy (FSHD), long non-protein coding RNA,Affinity proteomics

DavideGabellini
contact affiliation	Gene Expression and Muscular Dystrophy Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
contact email	gabellini.davide@hsr.it
lab head
AnnapaolaAndolfo
contact affiliation	Ospedale San Raffaele
contact email	andolfo.annapaola@hsr.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/04/PXD036038

PRIDE project URI

• PRIDE
  1. PXD036038
     1. Label: PRIDE project
     2. Name: Interactome of the long non-protein coding RNA (lncRNA) D4Z4 binding element-transcript (DBE-T)