Antagonistic regulation of Cyp26b1 by transcription factors SOX9/SF1 and FOXL2 during gonadal development in mice
Antagonistic regulation of Cyp26b1 by transcription factors SOX9/SF1 and FOXL2 during gonadal development in mice
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DOI：
10.1096/fj.11-184333
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发表时间：
2011-10-01
期刊：
影响因子：
4.8
通讯作者：
Koopman, Peter
中科院分区：
文献类型：
--
作者：
Kashimada, Kenichi;Svingen, Terje;Koopman, Peter
胎儿生殖细胞的性别决定取决于视黄酸 (RA) 暴露与睾丸特异性表达的分解代谢细胞色素 P450 酶 CYP26B1 所实现的 RA 降解之间的平衡。因此，鉴定调节Cyp26b1基因表达的因子是生殖生物学的一个重要目标。我们使用原位杂交证明 Cyp26b1 和转录因子基因类固醇生成因子 1 (Sf1) 和 Sry 相关的 HMG box 9 (Sox9) 在支持细胞中共表达，而 Cyp26b1 和 Sf1 在小鼠胎儿睾丸的 Leydig 细胞中共表达。在小鼠性腺体细胞系 TM3 中，表达 SOX9 和 SF1 的构建体的转染激活了 Cyp26b1 的表达，独立于正调节因子 RA。通过定量 RT-PCR (qRT-PCR) 测量，在 SOX9 或 SF1 缺陷的胚胎性腺中，Cyp26b1 表达相对于野生型 (WT) 对照降低。此外，qRT-PCR 显示，TM3 细胞中卵巢转录因子 Forkhead box L2 (FOXL2) 减弱了 SOX9/SF1 对 Cyp26b1 的上调，而在 Foxl2 缺失小鼠中，XX 性腺中的 Cyp26b1 表达相对于 WT 对照增加了 20 倍。这些数据支持这样的假设：SOX9 和 SF1 通过上调 Cyp26b1 来确保生殖细胞的雄性命运，而 FOXL2 可以拮抗卵巢中 Cyp26b1 的表达。-Kashimada, K.、Svingen, T.、Feng, C.-W.、Pelosi, E.、Bagheri-Fam, S.、Harley, V. R.、Schlessinger, D.、Bowles, J., Koopman, P. 在小鼠性腺发育过程中转录因子 SOX9/SF1 和 FOXL2 对 Cyp26b1 的拮抗调节。 FASEB J. 25, 3561-3569 (2011)。 www.fasebj.org
Sex determination in fetal germ cells depends on a balance between exposure to retinoic acid (RA) and the degradation of RA achieved by the testis-specific expression of the catabolic cytochrome P450 enzyme, CYP26B1. Therefore, identification of factors regulating the expression of the Cyp26b1 gene is an important goal in reproductive biology. We used in situ hybridization to demonstrate that Cyp26b1 and transcription factor genes steroidogenic factor-1 (Sf1) and Sry-related HMG box 9 (Sox9) are coexpressed in Sertoli cells, whereas Cyp26b1 and Sf1 are coexpressed in Leydig cells in mouse fetal testes. In the mouse gonadal somatic cell line TM3, transfection of constructs expressing SOX9 and SF1 activated Cyp26b1 expression, independently of the positive regulator RA. In embryonic gonads deficient in SOX9 or SF1, Cyp26b1 expression was decreased relative to wild-type (WT) controls, as measured by quantitative RT-PCR (qRT-PCR). Furthermore, qRT-PCR showed that Cyp26b1 up-regulation by SOX9/SF1 was attenuated by the ovarian transcription factor Forkhead box L2 (FOXL2) in TM3 cells, whereas in Foxl2-null mice, Cyp26b1 expression in XX gonads was increased similar to 20-fold relative to WT controls. These data support the hypothesis that SOX9 and SF1 ensure the male fate of germ cells by up-regulating Cyp26b1 and that FOXL2 acts to antagonize Cyp26b1 expression in ovaries.-Kashimada, K., Svingen, T., Feng, C.-W., Pelosi, E., Bagheri-Fam, S., Harley, V. R., Schlessinger, D., Bowles, J., Koopman, P. Antagonistic regulation of Cyp26b1 by transcription factors SOX9/SF1 and FOXL2 during gonadal development in mice. FASEB J. 25, 3561-3569 (2011). www.fasebj.org