SOX9 regulates expression of the male fertility gene Ets variant factor 5 (ETV5) during mammalian sex development

Alankarage, Dimuthu, Lavery, Rowena, Svingen, Terje, Kelly, Sabine, Ludbrook, Louisa, Bagheri-Fam, Stefan, Koopman, Peter and Harley, Vincent (2016) SOX9 regulates expression of the male fertility gene Ets variant factor 5 (ETV5) during mammalian sex development. International Journal of Biochemistry and Cell Biology, 79 41-51. doi:10.1016/j.biocel.2016.08.005


Author Alankarage, Dimuthu
Lavery, Rowena
Svingen, Terje
Kelly, Sabine
Ludbrook, Louisa
Bagheri-Fam, Stefan
Koopman, Peter
Harley, Vincent
Title SOX9 regulates expression of the male fertility gene Ets variant factor 5 (ETV5) during mammalian sex development
Formatted title
SOX9 regulates expression of the male fertility gene Ets variant factor 5 (ETV5) during mammalian sex development
Journal name International Journal of Biochemistry and Cell Biology   Check publisher's open access policy
ISSN 1878-5875
1357-2725
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1016/j.biocel.2016.08.005
Open Access Status Not yet assessed
Volume 79
Start page 41
End page 51
Total pages 11
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2017
Language eng
Formatted abstract
In humans, dysregulation of the sex determining gene SRY-box 9 (SOX9) leads to disorders of sex development (DSD). In mice, knock-out of Sox9 prior to sex determination leads to XY sex reversal, while Sox9 inactivation after sex determination leads to spermatogenesis defects. SOX9 specifies the differentiation and function of Sertoli cells from somatic cell precursors, which then orchestrate the development and maintenance of other testicular cell types, largely through unknown mechanisms. Here, we describe a novel testicular target gene of SOX9, Ets variant factor 5 (ETV5), a transcription factor responsible for maintaining the spermatogonial stem cell niche. Etv5 was highly expressed in wild-type XY but not XX mouse fetal gonads, with ETV5 protein localized in the Sertoli cells, interstitial cells and germ cells of the testis. In XY Sox9 knock-out gonads, Etv5 expression was strongly down-regulated. Similarly, knock-down of SOX9 in the human Sertoli-like cell line NT2/D1 caused a decrease in ETV5 gene expression. Transcriptomic analysis of NT2/D1 cells over-expressing SOX9 showed that ETV5 expression was increased in response to SOX9. Moreover, chromatin immunoprecipitation of these cells, as well as of embryonic mouse gonads, showed direct binding of SOX9 to ETV5 regulatory regions. We demonstrate that SOX9 was able to activate ETV5 expression via a conserved SOX site in the 5′ regulatory region, mutation of which led to loss of activation. In conclusion, we present a novel target gene of SOX9 in the testis, and suggest that SOX9 regulation of ETV5 contributes to the control of male fertility.
Keyword Disorders of sex development
DNA binding protein
Ets factor
Gene transcription
Male infertility
SOX proteins
Testis
Transcription regulation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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