Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland – involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1

Authors

  • Rok Košir,

    1.  Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
    Search for more papers by this author
    • These authors contributed equally to this work

  • Ursula Prosenc Zmrzljak,

    1.  Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
    Search for more papers by this author
    • These authors contributed equally to this work

  • Tanja Bele,

    1.  Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
    Search for more papers by this author
  • Jure Acimovic,

    1.  Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
    Search for more papers by this author
  • Martina Perse,

    1.  Medical Experimental Center, Institute of Pathology, University of Ljubljana, Slovenia
    Search for more papers by this author
  • Gregor Majdic,

    1.  Center for Animal Genomics, Veterinary Faculty, University of Ljubljana, Slovenia
    2.  Institute of Physiology, Faculty of Medicine, University of Maribor, Slovenia
    Search for more papers by this author
  • Cornelia Prehn,

    1.  Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
    Search for more papers by this author
  • Jerzy Adamski,

    1.  Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
    Search for more papers by this author
  • Damjana Rozman

    1.  Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
    Search for more papers by this author

D. Rozman, Institute of Biochemistry, Center for Functional Genomics and Biochips, Faculty of Medicine, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, Slovenia
Fax: +386 1 543 7588
Tel: +386 1 543 7591
E-mail: damjana.rozman@mf.uni-lj.si

Abstract

The cytochrome P450 (CYP) genes Cyp51, Cyp11a1, Cyp17a1, Cyb11b1, Cyp11b2 and Cyp21a1 are involved in the adrenal production of corticosteroids, whose circulating levels are circadian. cAMP signaling plays an important role in adrenal steroidogenesis. By using cAMP responsive element modulator (Crem) knockout mice, we show that CREM isoforms contribute to circadian expression of steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM-dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal glands. The data indicate that products of the Crem gene control the epigenetic repression of Cyp17 in mouse adrenal glands.

Ancillary