Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents

Missaghian, Elika; Kempná, Petra; Dick, Bernhard; Hirsch, Andrea; Alikhani-Koupaei, Rasoul; Jégou, Bernard; Mullis, Primus E; Frey, Brigitte M; Flück, Christa E (2009). Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents. Journal of endocrinology, 202(1), pp. 99-109. Bristol: BioScientifica 10.1677/JOE-08-0353

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The CYP17A1 gene is the qualitative regulator of steroidogenesis. Depending on the presence or absence of CYP17 activities mineralocorticoids, glucocorticoids or adrenal androgens are produced. The expression of the CYP17A1 gene is tissue as well as species-specific. In contrast to humans, adrenals of rodents do not express the CYP17A1 gene and have therefore no P450c17 enzyme for cortisol production, but produce corticosterone. DNA methylation is involved in the tissue-specific silencing of the CYP17A1 gene in human placental JEG-3 cells. We investigated the role of DNA methylation for the tissue-specific expression of the CYP17A1 gene in rodents. Rats treated with the methyltransferase inhibitor 5-aza-deoxycytidine excreted the cortisol metabolite tetrahydrocortisol in their urine suggesting that treatment induced CYP17 expression and 17alpha-hydroxylase activity through demethylation. Accordingly, bisulfite modification experiments identified a methylated CpG island in the CYP17 promoter in DNA extracted from rat adrenals but not from testes. Both methyltransferase and histone deacetylase inhibitors induced the expression of the CYP17A1 gene in mouse adrenocortical Y1 cells which normally do not express CYP17, indicating that the expression of the mouse CYP17A1 gene is epigenetically controlled. The role of DNA methylation for CYP17 expression was further underlined by the finding that a reporter construct driven by the mouse -1041 bp CYP17 promoter was active in Y1 cells, thus excluding the lack of essential transcription factors for CYP17 expression in these adrenal cells.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
UniBE Contributor:	Hirsch, Andrea, Mullis, Primus-Eugen, Frey, Brigitte, Flück Pandey, Christa Emma
ISSN:	0022-0795
Publisher:	BioScientifica
Language:	English
Submitter:	Anette van Dorland
Date Deposited:	04 Oct 2013 15:12
Last Modified:	02 Mar 2023 23:23
Publisher DOI:	10.1677/JOE-08-0353
PubMed ID:	19403566
Web of Science ID:	000272629500011
URI:	https://boris.unibe.ch/id/eprint/31843 (FactScience: 196589)