Transactivation of the Rat CYP2C13 Gene Promoter Involves HNF-1, HNF-3, and Members of the Orphan Receptor Subfamily

Catherine Legraverend; Hidetaka Eguchi; Anders Ström; Olivier Lahuna; Agneta Mode; Petra Tollet; Stefan Westin; Jan-Ake Gustafsson

doi:10.1021/bi00199a010

Transactivation of the Rat CYP2C13 Gene Promoter Involves HNF-1, HNF-3, and Members of the Orphan Receptor Subfamily

Catherine Legraverend, Hidetaka Eguchi, Anders Ström, Olivier Lahuna, Agneta Mode, Petra Tollet, Stefan Westin, Jan-Ake Gustafsson

Houston Methodist

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5′ flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-supported activity in non-liver cells.

Original language	English (US)
Pages (from-to)	9889-9897
Number of pages	9
Journal	Biochemistry
Volume	33
Issue number	33
DOIs	https://doi.org/10.1021/bi00199a010
State	Published - Aug 1 1994

ASJC Scopus subject areas

Biochemistry

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title = "Transactivation of the Rat CYP2C13 Gene Promoter Involves HNF-1, HNF-3, and Members of the Orphan Receptor Subfamily",

abstract = "The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5′ flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-supported activity in non-liver cells.",

author = "Catherine Legraverend and Hidetaka Eguchi and Anders Str{\"o}m and Olivier Lahuna and Agneta Mode and Petra Tollet and Stefan Westin and Jan-Ake Gustafsson",

year = "1994",

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doi = "10.1021/bi00199a010",

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pages = "9889--9897",

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T1 - Transactivation of the Rat CYP2C13 Gene Promoter Involves HNF-1, HNF-3, and Members of the Orphan Receptor Subfamily

AU - Legraverend, Catherine

AU - Eguchi, Hidetaka

AU - Ström, Anders

AU - Lahuna, Olivier

AU - Mode, Agneta

AU - Tollet, Petra

AU - Westin, Stefan

AU - Gustafsson, Jan-Ake

PY - 1994/8/1

Y1 - 1994/8/1

N2 - The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5′ flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-supported activity in non-liver cells.

AB - The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5′ flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-supported activity in non-liver cells.

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JO - Biochemistry

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Transactivation of the Rat CYP2C13 Gene Promoter Involves HNF-1, HNF-3, and Members of the Orphan Receptor Subfamily

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