Progesterone receptor mediates ovulatory transcription through RUNX transcription factor interactions and chromatin remodelling.

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dc.contributor.authorDinh, D.T.
dc.contributor.authorBreen, J.
dc.contributor.authorNicol, B.
dc.contributor.authorFoot, N.J.
dc.contributor.authorBersten, D.C.
dc.contributor.authorEmery, A.
dc.contributor.authorSmith, K.M.
dc.contributor.authorWong, Y.Y.
dc.contributor.authorBarry, S.C.
dc.contributor.authorYao, H.H.C.
dc.contributor.authorRobker, R.L.
dc.contributor.authorRussell, D.L.
dc.date.issued2023
dc.description.abstractProgesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation.
dc.description.statementofresponsibilityDoan T. Dinh, James Breen, Barbara Nicol, Natalie J. Foot, David C. Bersten, Alaknanda Emery, Kirsten M. Smith, Ying Y. Wong, Simon C. Barry, Humphrey H.C. Yao, Rebecca L. Robker, and Darryl L. Russell
dc.identifier.citationNucleic Acids Research, 2023; 51(12):5981-5996
dc.identifier.doi10.1093/nar/gkad271
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.orcidDinh, D.T. [0000-0002-6065-532X]
dc.identifier.orcidBreen, J. [0000-0001-6184-0925]
dc.identifier.orcidFoot, N.J. [0000-0002-6567-9283]
dc.identifier.orcidBersten, D.C. [0000-0003-4952-959X]
dc.identifier.orcidSmith, K.M. [0000-0001-7505-778X]
dc.identifier.orcidWong, Y.Y. [0000-0002-3472-5080]
dc.identifier.orcidBarry, S.C. [0000-0002-0597-7609]
dc.identifier.orcidRobker, R.L. [0000-0002-1538-4604]
dc.identifier.orcidRussell, D.L. [0000-0002-4930-7658]
dc.identifier.urihttps://hdl.handle.net/2440/139091
dc.language.isoen
dc.publisherOxford University Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1110562
dc.rightsPublished by Oxford University Press on behalf of Nucleic Acids Research 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.
dc.source.urihttps://doi.org/10.1093/nar/gkad271
dc.subjectChromatin
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMammals
dc.subjectMice
dc.subjectReceptors, Progesterone
dc.subjectTranscription Factors
dc.subjectChromatin Assembly and Disassembly
dc.subjectTranscription, Genetic
dc.subjectGene Expression Regulation
dc.subjectFemale
dc.subjectCore Binding Factor Alpha 2 Subunit
dc.subject.meshChromatin
dc.subject.meshAnimals
dc.subject.meshMice, Knockout
dc.subject.meshMammals
dc.subject.meshMice
dc.subject.meshReceptors, Progesterone
dc.subject.meshTranscription Factors
dc.subject.meshChromatin Assembly and Disassembly
dc.subject.meshTranscription, Genetic
dc.subject.meshGene Expression Regulation
dc.subject.meshFemale
dc.subject.meshCore Binding Factor Alpha 2 Subunit
dc.titleProgesterone receptor mediates ovulatory transcription through RUNX transcription factor interactions and chromatin remodelling.
dc.typeJournal article
pubs.publication-statusPublished

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