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Transcriptional regulation of human CYP11A1 in gonads and adrenals

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Journal of Biomedical Science

Summary

The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme, also termed cytochrome P450scc, which catalyzes the conversion of cholesterol to pregnenolone in the first step of steroid biosynthesis in mitochondria. The adrenal- and gonad-selective, hormonally and developmentally regulated expression of CYP11A1 is principally driven by its 2.3 kb promoter. Multiple trans-acting factors like SF-1, Sp1, AP-2, TReP-132, LBP-1b, LBP-9, AP-1, NF-1, and Ets control CYP11A1 transcription either through DNA-protein interaction with their specific cis-acting elements or through protein-protein interaction between each other, wherein SF-1 plays a central role in adrenals and testes. In addition to binding with its proximal and upstream motifs, SF-1 also physically interacts with TFIIB, CBP/p300, TReP-132, and c-Jun/AP-1 to specifically transmit the regulatory signals of cAMP. Other factors like Sp1 family members, AP-2, and LBP-1b/LBP-9 may be other factors that play a role in CYP11A1 transcription, particularly in placental cells. The TATA sequence could also contribute to tissue-specificity and hormonal regulation of CYP11A1 transcription. This article reviews recent studies focusing on adrenals and gonads.

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Acknowledgments

We would like to thank Transgenic Core Facility at Academia Sinica for the generation of transgenic and knockout mouse lines. This work was supported by the National Taiwan University (to I.-C. Guo), and by grants NSC94-2311-B-001-039 (to B.-c. Chung) and NSC95-2313-B002-061-MY3 (to I.-C. Guo) from the National Science Council, and DOH95-TD-HF-111-003(1/3) (to I.-C. Guo) from the Department of Health, Executive Yuan, and AS92IMB4PP (to B.-c. Chung) from Academia Sinica, Republic of China.

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Authors and Affiliations

  1. Department of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan

    Ing-Cherng Guo

  2. Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 115, Taiwan

    Meng-Chun Shih, Hsin-Chieh Lan, Nai-Chi Hsu & Bon-chu Chung

  3. Institutes of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan

    Meng-Chun Shih

  4. Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan

    Meng-Chun Hu

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  1. Ing-Cherng Guo
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Correspondence to Bon-chu Chung.

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This article is for the Special Issue of IMB 20th anniversary.

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Guo, IC., Shih, MC., Lan, HC. et al. Transcriptional regulation of human CYP11A1 in gonads and adrenals. J Biomed Sci 14, 509–515 (2007). https://doi.org/10.1007/s11373-007-9177-z

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  • DOI: https://doi.org/10.1007/s11373-007-9177-z

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