In mammalian foetal testes, SOX9 regulates expression of its target genes by binding to genomic regions with conserved signatures

Massilva Rahmoun, Rowena Lavery, Sabine Laurent-Chaballier, Nicolas Bellora, Gayle K. Philip, Moïra Rossitto, Aleisha Symon, Eric Pailhoux, Florence Cammas, Jessica Chung, Stefan Bagheri-Fam, Mark Murphy, Vivian Bardwell, David Zarkower, Brigitte Boizet-Bonhoure, Philippe Clair, Vincent R. Harley, Francis Poulat

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

In mammalian embryonic gonads, SOX9 is required for the determination of Sertoli cells that orchestrate testis morphogenesis. To identify genetic networks directly regulated by SOX9, we combined analysis of SOX9-bound chromatin regions from murine and bovine foetal testes with sequencing of RNA samples from mouse testes lacking Sox9. We found that SOX9 controls a conserved genetic programme that involves most of the sex-determining genes. In foetal testes, SOX9 modulates both transcription and directly or indirectly sex-specific differential splicing of its target genes through binding to genomic regions with sequence motifs that are conserved among mammals and that we called 'Sertoli Cell Signature' (SCS). The SCS is characterized by a precise organization of binding motifs for the Sertoli cell reprogramming factors SOX9, GATA4 and DMRT1. As SOX9 biological role in mammalian gonads is to determine Sertoli cells, we correlated this genomic signature with the presence of SOX9 on chromatin in foetal testes, therefore equating this signature to a genomic bar code of the fate of foetal Sertoli cells. Starting from the hypothesis that nuclear factors that bind to genomic regions with SCS could functionally interact with SOX9, we identified TRIM28 as a new SOX9 partner in foetal testes.

Original languageEnglish (US)
Pages (from-to)7191-7211
Number of pages21
JournalNucleic acids research
Volume45
Issue number12
DOIs
StatePublished - Jul 1 2017

Bibliographical note

Funding Information:
Agence Nationale pour la Recherche (ANR blanc Testis- Dev to B.B. and F.P.); National Health and Medical Research Council Program [1074258 to V.R.H.]; National Health and Medical Research Council Fellowship [1020034 to V.R.H.]; Victorian Government's Operational Infrastructure Support Program (to V.R.H.); Australian Postgraduate Award (to A.S.). Funding for open access charge: Agence Nationale pour la Recherche.

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