Document Detail

Sox9 gene regulation and the loss of the XY/XX sex-determining mechanism in the mole vole Ellobius lutescens.
MedLine Citation:
PMID:  22215485     Owner:  NLM     Status:  MEDLINE    
In most mammals, the Y chromosomal Sry gene initiates testis formation within the bipotential gonad, resulting in male development. SRY is a transcription factor and together with SF1 it directly up-regulates the expression of the pivotal sex-determining gene Sox9 via a 1.3-kb cis-regulatory element (TESCO) which contains an evolutionarily conserved region (ECR) of 180 bp. Remarkably, several rodent species appear to determine sex in the absence of Sry and a Y chromosome, including the mole voles Ellobius lutescens and Ellobius tancrei, whereas Ellobius fuscocapillus of the same genus retained Sry. The sex-determining mechanisms in the Sry-negative species remain elusive. We have cloned and sequenced 1.1 kb of E. lutescens TESCO which shares 75% sequence identity with mouse TESCO indicating that testicular Sox9 expression in E. lutescens might still be regulated via TESCO. We have also cloned and sequenced the ECRs of E. tancrei and E. fuscocapillus. While the three Ellobius ECRs are highly similar (94-97% sequence identity), they all display a 14-bp deletion (Δ14) removing a highly conserved SOX/TCF site. Introducing Δ14 into mouse TESCO increased both basal activity and SF1-mediated activation of TESCO in HEK293T cells. We propose a model whereby Δ14 may have triggered up-regulation of Sox9 in XX gonads leading to destabilization of the XY/XX sex-determining mechanism in Ellobius. E. lutescens/E. tancrei and E. fuscocapillus could have independently stabilized their sex determination mechanisms by Sry-independent and Sry-dependent approaches, respectively.
Stefan Bagheri-Fam; Rajini Sreenivasan; Pascal Bernard; Kevin C Knower; Ryohei Sekido; Robin Lovell-Badge; Walter Just; Vincent R Harley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology     Volume:  20     ISSN:  1573-6849     ISO Abbreviation:  Chromosome Res.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-02-21     Completed Date:  2012-06-07     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9313452     Medline TA:  Chromosome Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  191-9     Citation Subset:  IM    
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MeSH Terms
Arvicolinae / genetics*,  metabolism,  physiology
Base Sequence
Binding Sites
Cloning, Molecular
Conserved Sequence
Evolution, Molecular
Gene Expression Regulation*
Genetic Variation
Genetic Vectors / genetics,  metabolism
HEK293 Cells
Models, Genetic
Molecular Sequence Data
Mutagenesis, Site-Directed
SOX9 Transcription Factor / genetics,  metabolism*
Sequence Alignment
Sequence Analysis, DNA
Sequence Deletion
Sex Determination Processes*
Testis / cytology,  metabolism,  physiology
Y Chromosome / genetics,  metabolism*
Grant Support
MC_U117562207//Medical Research Council
Reg. No./Substance:
0/SOX9 Transcription Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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