Journal Article

Binding of Steroidogenic Factor-1 to the Regulatory Region Might Not Be Critical for Transcriptional Regulation of the Human <i>CYP1B1</i> Gene

Yuki Tsuchiya, Miki Nakajima, Shingo Takagi, Miki Katoh, Wenchao Zheng, Colin R Jefcoate and Tsuyoshi Yokoi

in The Journal of Biochemistry

Published on behalf of The Japanese Biochemical Society

Volume 139, issue 3, pages 527-534
Published in print March 2006 | ISSN: 0021-924X
Published online March 2006 | e-ISSN: 1756-2651 | DOI: http://dx.doi.org/10.1093/jb/mvj055
Binding of Steroidogenic Factor-1 to the Regulatory Region Might Not Be Critical for Transcriptional Regulation of the Human CYP1B1 Gene

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Cytochrome P450 (CYP) 1B1, which catalyzes 17β-estradiol 4-hydroxylation, is expressed in steroid-related tissues including ovary, testis, and adrenal gland. Generally, the expressions of steroidogenic CYPs are transcriptionally regulated by steroidogenic factor-1 (SF-1) and cAMP response element (CRE) binding protein (CREB). In the present study, we examined the possibility that the human CYP1B1 gene might be regulated by SF-1 and CREB. Gel shift analyses revealed that in vitro translated SF-1 can bind to the putative SF-1 binding sites, SF-1a (at –1722) and SF-1b (at –2474), on the CYP1B1 gene. In vitro translated CREB barely binds to the putative SF-1 binding sites. Luciferase analysis revealed that a reporter plasmid, pGL3 (–2623/+25), containing the SF-1a and SF-1b elements is transactivated by the concomitant co-expression of SF-1 and protein kinase A (PKA). However, the transcriptional activity is induced by PKA alone. Mutations in the SF-1a and SF-1b elements did not affect the luciferase activity. Thus, the binding of SF-1 to the putative SF-1 binding sites of the human CYP1B1 gene might not be essential for transcriptional regulation. Interestingly, deletion and mutation analyses indicated that the PKA signaling pathway is involved in the xenobiotic responsive element (XRE)–mediated transactivation of the human CYP1B1 gene.

Keywords: CREB; CYP1B1; gene regulation; PKA; SF-1; AhR, aryl hydrocarbon receptor; ARNT, AhR nuclear translocator; CRE, cAMP response element; CREB, CRE binding protein; CYP, cytochrome P450; PKA, protein kinase A; SF-1, steroidogenic factor-1; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; XRE, xenobiotic responsive element

Journal Article.  5379 words.  Illustrated.

Subjects: Biochemistry

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