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

Identifieur interne : 000A07 ( Main/Exploration ); précédent : 000A06; suivant : 000A08

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

Auteurs : Massilva Rahmoun [France] ; Rowena Lavery [Australie] ; Sabine Laurent-Chaballier [France] ; Nicolas Bellora [Argentine] ; Gayle K. Philip [Australie] ; Moïra Rossitto [France] ; Aleisha Symon [Australie] ; Eric Pailhoux [France] ; Florence Cammas [France] ; Jessica Chung [Australie] ; Stefan Bagheri-Fam [Australie] ; Mark Murphy [États-Unis] ; Vivian Bardwell [États-Unis] ; David Zarkower [États-Unis] ; Brigitte Boizet-Bonhoure [France] ; Philippe Clair [France] ; Vincent R. Harley [Australie] ; Francis Poulat [France]

Source :

RBID : PMC:5499551

Descripteurs français

English descriptors

Abstract

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.


Url:
DOI: 10.1093/nar/gkx328
PubMed: 28472341
PubMed Central: 5499551


Affiliations:


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<wicri:regionArea>VLSCI, LAB-14, 700 Swanston Street, Carlton 3053, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bagheri Fam, Stefan" sort="Bagheri Fam, Stefan" uniqKey="Bagheri Fam S" first="Stefan" last="Bagheri-Fam">Stefan Bagheri-Fam</name>
<affiliation wicri:level="3">
<nlm:aff id="AFF2">The Hudson Institute of Medical Research and Department of Anatomy, Monash University, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Hudson Institute of Medical Research and Department of Anatomy, Monash University, Melbourne</wicri:regionArea>
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<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Murphy, Mark" sort="Murphy, Mark" uniqKey="Murphy M" first="Mark" last="Murphy">Mark Murphy</name>
<affiliation wicri:level="2">
<nlm:aff id="AFF7">Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson hall, 321 Church St, SE, Minneapolis, MN 55455, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson hall, 321 Church St, SE, Minneapolis, MN 55455</wicri:regionArea>
<placeName>
<region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Bardwell, Vivian" sort="Bardwell, Vivian" uniqKey="Bardwell V" first="Vivian" last="Bardwell">Vivian Bardwell</name>
<affiliation wicri:level="2">
<nlm:aff id="AFF7">Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson hall, 321 Church St, SE, Minneapolis, MN 55455, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson hall, 321 Church St, SE, Minneapolis, MN 55455</wicri:regionArea>
<placeName>
<region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zarkower, David" sort="Zarkower, David" uniqKey="Zarkower D" first="David" last="Zarkower">David Zarkower</name>
<affiliation wicri:level="2">
<nlm:aff id="AFF7">Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson hall, 321 Church St, SE, Minneapolis, MN 55455, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson hall, 321 Church St, SE, Minneapolis, MN 55455</wicri:regionArea>
<placeName>
<region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Boizet Bonhoure, Brigitte" sort="Boizet Bonhoure, Brigitte" uniqKey="Boizet Bonhoure B" first="Brigitte" last="Boizet-Bonhoure">Brigitte Boizet-Bonhoure</name>
<affiliation wicri:level="3">
<nlm:aff id="AFF1">Institute of Human Genetics, CNRS-University of Montpellier UMR9002, 34396 Montpellier cedex 5, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institute of Human Genetics, CNRS-University of Montpellier UMR9002, 34396 Montpellier cedex 5</wicri:regionArea>
<placeName>
<region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Languedoc-Roussillon</region>
<settlement type="city">Montpellier</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Clair, Philippe" sort="Clair, Philippe" uniqKey="Clair P" first="Philippe" last="Clair">Philippe Clair</name>
<affiliation wicri:level="3">
<nlm:aff id="AFF8">University of Montpellier, Montpellier GenomiX, bat 24, Place Eugène Bataillon, 34095 Montpellier cedex 5, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Montpellier, Montpellier GenomiX, bat 24, Place Eugène Bataillon, 34095 Montpellier cedex 5</wicri:regionArea>
<placeName>
<region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Languedoc-Roussillon</region>
<settlement type="city">Montpellier</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Harley, Vincent R" sort="Harley, Vincent R" uniqKey="Harley V" first="Vincent R." last="Harley">Vincent R. Harley</name>
<affiliation wicri:level="3">
<nlm:aff id="AFF2">The Hudson Institute of Medical Research and Department of Anatomy, Monash University, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Hudson Institute of Medical Research and Department of Anatomy, Monash University, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Poulat, Francis" sort="Poulat, Francis" uniqKey="Poulat F" first="Francis" last="Poulat">Francis Poulat</name>
<affiliation wicri:level="3">
<nlm:aff id="AFF1">Institute of Human Genetics, CNRS-University of Montpellier UMR9002, 34396 Montpellier cedex 5, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institute of Human Genetics, CNRS-University of Montpellier UMR9002, 34396 Montpellier cedex 5</wicri:regionArea>
<placeName>
<region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Languedoc-Roussillon</region>
<settlement type="city">Montpellier</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Nucleic Acids Research</title>
<idno type="ISSN">0305-1048</idno>
<idno type="eISSN">1362-4962</idno>
<imprint>
<date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Cattle</term>
<term>Chromatin (chemistry)</term>
<term>Chromatin (metabolism)</term>
<term>Embryo, Mammalian</term>
<term>Female</term>
<term>Fetus</term>
<term>GATA4 Transcription Factor (genetics)</term>
<term>GATA4 Transcription Factor (metabolism)</term>
<term>Gene Expression Regulation, Developmental</term>
<term>Gene Regulatory Networks</term>
<term>Male</term>
<term>Mice</term>
<term>Morphogenesis (genetics)</term>
<term>Nuclear Proteins (genetics)</term>
<term>Nuclear Proteins (metabolism)</term>
<term>Protein Binding</term>
<term>Repressor Proteins (genetics)</term>
<term>Repressor Proteins (metabolism)</term>
<term>SOX9 Transcription Factor (genetics)</term>
<term>SOX9 Transcription Factor (metabolism)</term>
<term>Sequence Analysis, RNA</term>
<term>Sertoli Cells (cytology)</term>
<term>Sertoli Cells (metabolism)</term>
<term>Sex Determination Processes</term>
<term>Transcription Factors (genetics)</term>
<term>Transcription Factors (metabolism)</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Analyse de séquence d'ARN</term>
<term>Animaux</term>
<term>Bovins</term>
<term>Cellules de Sertoli (cytologie)</term>
<term>Cellules de Sertoli (métabolisme)</term>
<term>Chromatine ()</term>
<term>Chromatine (métabolisme)</term>
<term>Embryon de mammifère</term>
<term>Facteur de transcription GATA-4 (génétique)</term>
<term>Facteur de transcription GATA-4 (métabolisme)</term>
<term>Facteur de transcription SOX-9 (génétique)</term>
<term>Facteur de transcription SOX-9 (métabolisme)</term>
<term>Facteurs de transcription (génétique)</term>
<term>Facteurs de transcription (métabolisme)</term>
<term>Femelle</term>
<term>Foetus</term>
<term>Liaison aux protéines</term>
<term>Morphogenèse (génétique)</term>
<term>Mâle</term>
<term>Processus de détermination du sexe</term>
<term>Protéines de répression (génétique)</term>
<term>Protéines de répression (métabolisme)</term>
<term>Protéines nucléaires (génétique)</term>
<term>Protéines nucléaires (métabolisme)</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
<term>Réseaux de régulation génique</term>
<term>Souris</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Chromatin</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>GATA4 Transcription Factor</term>
<term>Nuclear Proteins</term>
<term>Repressor Proteins</term>
<term>SOX9 Transcription Factor</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Chromatin</term>
<term>GATA4 Transcription Factor</term>
<term>Nuclear Proteins</term>
<term>Repressor Proteins</term>
<term>SOX9 Transcription Factor</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Cellules de Sertoli</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Sertoli Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Morphogenesis</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Facteur de transcription GATA-4</term>
<term>Facteur de transcription SOX-9</term>
<term>Facteurs de transcription</term>
<term>Morphogenèse</term>
<term>Protéines de répression</term>
<term>Protéines nucléaires</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Sertoli Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cellules de Sertoli</term>
<term>Chromatine</term>
<term>Facteur de transcription GATA-4</term>
<term>Facteur de transcription SOX-9</term>
<term>Facteurs de transcription</term>
<term>Protéines de répression</term>
<term>Protéines nucléaires</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cattle</term>
<term>Embryo, Mammalian</term>
<term>Female</term>
<term>Fetus</term>
<term>Gene Expression Regulation, Developmental</term>
<term>Gene Regulatory Networks</term>
<term>Male</term>
<term>Mice</term>
<term>Protein Binding</term>
<term>Sequence Analysis, RNA</term>
<term>Sex Determination Processes</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse de séquence d'ARN</term>
<term>Animaux</term>
<term>Bovins</term>
<term>Chromatine</term>
<term>Embryon de mammifère</term>
<term>Femelle</term>
<term>Foetus</term>
<term>Liaison aux protéines</term>
<term>Mâle</term>
<term>Processus de détermination du sexe</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
<term>Réseaux de régulation génique</term>
<term>Souris</term>
<term>Transcriptome</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<title>Abstract</title>
<p>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
<italic>Sox9</italic>
. 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.</p>
</div>
</front>
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</country>
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<li>Languedoc-Roussillon</li>
<li>Minnesota</li>
<li>Occitanie (région administrative)</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
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<li>Melbourne</li>
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<name sortKey="Clair, Philippe" sort="Clair, Philippe" uniqKey="Clair P" first="Philippe" last="Clair">Philippe Clair</name>
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<name sortKey="Rossitto, Moira" sort="Rossitto, Moira" uniqKey="Rossitto M" first="Moïra" last="Rossitto">Moïra Rossitto</name>
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<name sortKey="Philip, Gayle K" sort="Philip, Gayle K" uniqKey="Philip G" first="Gayle K." last="Philip">Gayle K. Philip</name>
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<name sortKey="Bellora, Nicolas" sort="Bellora, Nicolas" uniqKey="Bellora N" first="Nicolas" last="Bellora">Nicolas Bellora</name>
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<region name="Minnesota">
<name sortKey="Murphy, Mark" sort="Murphy, Mark" uniqKey="Murphy M" first="Mark" last="Murphy">Mark Murphy</name>
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