The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice

Bradford, S. T., Hiramatsu, R, Maddugoda, M. P., Bernard, P, Chaboissier, M. C., Sinclair, A, Schedl, A, Harley, V, Kanai, Y, Koopman, P and Wilhelm, D (2009) The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice. Biology of Reproduction, 80 6: 1178-1188. doi:10.1095/biolreprod.108.071480

Author Bradford, S. T.
Hiramatsu, R
Maddugoda, M. P.
Bernard, P
Chaboissier, M. C.
Sinclair, A
Schedl, A
Harley, V
Kanai, Y
Koopman, P
Wilhelm, D
Title The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice
Journal name Biology of Reproduction   Check publisher's open access policy
ISSN 0006-3363
Publication date 2009-06-01
Year available 2009
Sub-type Article (original research)
DOI 10.1095/biolreprod.108.071480
Open Access Status Not Open Access
Volume 80
Issue 6
Start page 1178
End page 1188
Total pages 11
Editor John J Eppig
Place of publication Madison, WI, U.S.A.
Publisher Society for the Study of Reproduction
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Abstract In most mammals, the expression of SRY (sex-determining region on the Y chromosome) initiates the development of testes, and thus determines the sex of the individual. However, despite the pivotal role of SRY, its mechanism of action remains elusive. One important missing piece of the puzzle is the identification of genes regulated by SRY. In this study we used chromatin immunoprecipitation to identify direct SRY target genes. Anti-mouse SRY antibody precipitated a region 7.5 kb upstream of the transcriptional start site of cerebellin 4 precursor (Cbln4), which encodes a secreted protein. Cbln4 is expressed in Sertoli cells in the developing gonad, with a profile mimicking that of the testis-determining gene SRY-box containing gene 9 (Sox9). In transgenic XY mouse embryos with reduced Sox9 expression, Cbln4 expression also was reduced, whereas overexpression of Sox9 in XX mice caused an upregulation of Cbln4 expression. Finally, ectopic upregulation of SRY in vivo resulted in ectopic expression of Cbln4. Our findings suggest that both SRY and SOX9 contribute to the male-specific upregulation of Cbln4 in the developing testis, and they identified a direct in vivo target gene of SRY.
Keyword Cbln4
Mammalian Sex Determination
developmental biology
gene regulation
Sertoli cells
sex determination
transcriptional regulation
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID R03-HD049431
Institutional Status UQ
Additional Notes Published ahead of print February 11, 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 18:07:27 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience