PXD043951-2

PXD043951 is an original dataset announced via ProteomeXchange.

Title	FOXL2 interaction with different binding partners regulates the dynamics of granulosa cell differentiation across ovarian development
Description	FOXL2 is a transcription factor essential for female fertility, expressed in somatic cells of the ovary, notably granulosa cells. In the mouse, Foxl2 deletion leads to partial sex reversal postnatally. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation. We hypothesised that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played across ovarian development. Therefore, we characterised the dynamics of gene expression and chromatin accessibility changes in purified murine granulosa cells across key developmental stages (E14.5, 1 and 8 weeks). We then performed genome-wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP. We found that FOXL2 regulates more genes at postnatal stages, through the interaction with factors regulating primordial follicle activation (PFA), such as NR5A2, and others regulating steroidogenesis including AR and ESR2. As a proof of principle experiment, we chose one FOXL2 interactor, Ubiquitin specific protease 7 (USP7) and showed that deletion of this gene in granulosa cells leads to a blockage of PFA, impaired ovary development and sterility. Our study constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:34:24.221.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roberta Migale
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-20 05:47:38	ID requested
1	2024-03-25 04:11:09	announced
⏵ 2	2024-10-22 06:34:24	announced	2024-10-22: Updated project metadata.

10.1126/SCIADV.ADL0788;

submitter keyword: ovary, ChIP-SICAP, FOXL2

Robin Lovell-Badge
contact affiliation	Stem cell and developmental genetics laboratory, The Francis Crick Institute, London, UK
contact email	robin.lovell-badge@crick.ac.uk
lab head
Roberta Migale
contact affiliation	The Francis Crick Institute
contact email	roberta.migale@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043951
     1. Label: PRIDE project
     2. Name: FOXL2 interaction with different binding partners regulates the dynamics of granulosa cell differentiation across ovarian development