Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1

Erling A. Hoivik, Linda Aumo, Reidun Aesoy, Haldis Lillefosse, Aurélia E. Lewis, Rebecca M. Perrett, Nancy R. Stallings, Neil A. Hanley, Marit Bakke

Research output: Contribution to journalArticle

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Abstract

Steroidogenic factor 1 (SF1) is expressed in a time- and cell-specific manner in the endocrine system. In this study we present evidence to support that methylation of CpG sites located in the proximal promoter of the gene encoding SF1 contributes to the restricted expression pattern of this nuclear receptor. DNA methylation analyses revealed a nearly perfect correlation between the methylation status of the proximal promoter and protein expression, such that it was hypomethylated in cells that express SF1 but hypermethylated in nonexpressing cells. Moreover, in vitro methylation of this region completely repressed reporter gene activity in transfected steroidogenic cells. Bisulfite sequencing of DNA from embryonic tissue demonstrated that the proximal promoter was unmethylated in the developing testis and ovary, whereas it was hypermethylated in tissues that do not express SF1. Together these results indicate that the DNA methylation pattern is established early in the embryo and stably inherited thereafter throughout development to confine SF1 expression to the appropriate tissues. Chromatin immunoprecipitation analyses revealed that the transcriptional activator upstream stimulatory factor 2 and RNA polymerase II were specifically recruited to this DNA region in cells in which the proximal promoter is hypomethylated, providing functional support for the fact that lack of methylation corresponds to a transcriptionally active gene. In conclusion, we identified a region within the SF1/Sf1 gene that epigenetically directs cell-specific expression of SF1.

Original languageEnglish (US)
Pages (from-to)5599-5609
Number of pages11
JournalEndocrinology
Volume149
Issue number11
DOIs
StatePublished - Nov 2008

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Steroidogenic Factor 1
Methylation
DNA
DNA Methylation
Upstream Stimulatory Factors
Genes
Endocrine System
RNA Polymerase II
Chromatin Immunoprecipitation
Cytoplasmic and Nuclear Receptors
DNA Sequence Analysis
Reporter Genes
Testis
Ovary
Embryonic Structures

ASJC Scopus subject areas

  • Endocrinology

Cite this

Hoivik, E. A., Aumo, L., Aesoy, R., Lillefosse, H., Lewis, A. E., Perrett, R. M., ... Bakke, M. (2008). Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1. Endocrinology, 149(11), 5599-5609. https://doi.org/10.1210/en.2008-0104

Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1. / Hoivik, Erling A.; Aumo, Linda; Aesoy, Reidun; Lillefosse, Haldis; Lewis, Aurélia E.; Perrett, Rebecca M.; Stallings, Nancy R.; Hanley, Neil A.; Bakke, Marit.

In: Endocrinology, Vol. 149, No. 11, 11.2008, p. 5599-5609.

Research output: Contribution to journalArticle

Hoivik, EA, Aumo, L, Aesoy, R, Lillefosse, H, Lewis, AE, Perrett, RM, Stallings, NR, Hanley, NA & Bakke, M 2008, 'Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1', Endocrinology, vol. 149, no. 11, pp. 5599-5609. https://doi.org/10.1210/en.2008-0104
Hoivik EA, Aumo L, Aesoy R, Lillefosse H, Lewis AE, Perrett RM et al. Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1. Endocrinology. 2008 Nov;149(11):5599-5609. https://doi.org/10.1210/en.2008-0104
Hoivik, Erling A. ; Aumo, Linda ; Aesoy, Reidun ; Lillefosse, Haldis ; Lewis, Aurélia E. ; Perrett, Rebecca M. ; Stallings, Nancy R. ; Hanley, Neil A. ; Bakke, Marit. / Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1. In: Endocrinology. 2008 ; Vol. 149, No. 11. pp. 5599-5609.
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