Multiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsy

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dc.contributor.authorde Nys, R.
dc.contributor.authorvan Eyk, C.L.
dc.contributor.authorRitchie, T.
dc.contributor.authorMøller, R.S.
dc.contributor.authorScheffer, I.E.
dc.contributor.authorMarini, C.
dc.contributor.authorBhattacharjee, R.
dc.contributor.authorKumar, R.
dc.contributor.authorGecz, J.
dc.date.issued2024
dc.description.abstractClustering Epilepsy (CE) is an epileptic disorder with neurological comorbidities caused by heterozygous variants of the X chromosome gene Protocadherin 19 (PCDH19). Recent studies have implicated dysregulation of the Nuclear Hormone Receptor (NHR) pathway in CE pathogenesis. To obtain a comprehensive overview of the impact and mechanisms of loss of PCDH19 function in CE pathogenesis, we have performed epigenomic, transcriptomic and proteomic analysis of CE relevant models. Our studies identified differential regulation and expression of Androgen Receptor (AR) and its targets in CE patient skin fibroblasts. Furthermore, our cell culture assays revealed the repression of PCDH19 expression mediated through ERα and the co-regulator FOXA1. We also identified a protein-protein interaction between PCDH19 and AR, expanding upon the intrinsic link between PCDH19 and the NHR pathway. Together, these results point to a novel mechanism of NHR signaling in the pathogenesis of CE that can be explored for potential therapeutic options.
dc.description.statementofresponsibilityRebekah de Nys, Clare L. van Eyk, Tarin Ritchie, Rikke S. Møller, Ingrid E. Scheffer, Carla Marini, Rudrarup Bhattacharjee, Raman Kumar, and Jozef Gecz
dc.identifier.citationTranslational Psychiatry, 2024; 14(1):1-9
dc.identifier.doi10.1038/s41398-024-02783-5
dc.identifier.issn2158-3188
dc.identifier.issn2158-3188
dc.identifier.orcidvan Eyk, C.L. [0000-0003-0345-9944]
dc.identifier.orcidRitchie, T. [0000-0003-2951-6820]
dc.identifier.orcidBhattacharjee, R. [0000-0003-2740-6986]
dc.identifier.orcidKumar, R. [0000-0001-7976-8386]
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.urihttps://hdl.handle.net/2440/140414
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2010562
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1155224
dc.rights© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/.
dc.source.urihttp://dx.doi.org/10.1038/s41398-024-02783-5
dc.subjectCadherins
dc.subjectCluster Analysis
dc.subjectEpilepsy
dc.subjectHumans
dc.subjectMultiomics
dc.subjectProteomics
dc.subjectProtocadherins
dc.subjectMedical genetics
dc.subjectmolecular neuroscience
dc.subjectpsychiatric disorders
dc.subject.meshHumans
dc.subject.meshEpilepsy
dc.subject.meshCadherins
dc.subject.meshCluster Analysis
dc.subject.meshProteomics
dc.subject.meshProtocadherins
dc.subject.meshMultiomics
dc.titleMultiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsy
dc.typeJournal article
pubs.publication-statusPublished

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