Proteomics and transcriptome approaches to investigate the mechanism of human sex determination.
The SRY gene (sex-determining region on the Y chromosome) was isolated in 1990 and is known as the testis-determining factor on the Y chromosome. The SRY has been considered as a transcription factor since it contains an HMG box, which functions as a DNA-binding domain. However, a direct target for SRY remains to be identified. We have investigated the function of SRY through proteomics and transcriptome approaches, and by using two stable SRY-overexpressing cell lines (SRY1 and SRY2) in NT2/D1 cells derived from human testicular embryonal cell carcinoma. The results of 2-dimensional gel electrophoresis show that SRY overexpression causes a considerable downregulation of many chaperone proteins. SRY also upregulates laminin, which is important for Sertoli cell differentiation. Additionally, transcriptome analysis shows that SRY overexpression upregulates many zinc finger proteins and downregulates cellular growth factors with S or G(2)/M arrest of the cell cycle and inhibition of cellular proliferation.
Department of Human Genetics and Public Health, Graduate School of Proteomics, Faculty of Medicine, University of Tokushima, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan. sato@basic.med.tokushima-u.ac.jp
Youichi
Y
Sato
Toshikatsu
T
Shinka
Gang
G
Chen
Hong-Tao
HT
Yan
Kozue
K
Sakamoto
Ashraf A
AA
Ewis
Hiroyuki
H
Aburatani
Yutaka
Y
Nakahori
D002455:Cell Division; D045744:Cell Line, Tumor; D041322:Chromosomes, Human, Y; D016195:G2 Phase; D020869:Gene Expression Profiling / Q000379:methods*; D024282:Genes, sry; D006801:Humans; D007797:Laminin / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D016196:S Phase; D019849:Sex Determination Processes
D007797:Laminin