CpG dinucleotide methylation of the CYP19 I.3/II promoter modulates cAMP-stimulated aromatase activity

Molecular and Cellular Endocrinology
Masashi Demura, Serdar E Bulun

Abstract

Aromatase expression varies in a tissue-specific manner and among individuals. Aromatase promoter I.3/II, regulated by a cAMP response element (CRE), is normally quiescent in human skin fibroblasts, whereas its hyperactivity may cause local or systemic estrogen excess. We describe the methylation status of 6 CpG dinucleotides within a 571-bp fragment of promoter I.3/II containing a CRE in cAMP-responsive (n=1) or nonresponsive (n=3) primary skin fibroblasts cultured from healthy volunteers. Four out of 6 CpG dinucleotides were unmethylated in cAMP-responsive fibroblasts, whereas all 6 CpG dinucleotides were hypermethylated in cAMP-nonresponsive fibroblasts. Basal and cAMP-stimulated aromatase activity and promoter I.3/II activation were significantly higher in the presence of unmethylated DNA. Furthermore, methylation at the CRE interfered with CREB binding. Thus, methylation of CpG dinucleotides within promoter I.3/II regulates aromatase expression and may be one source of inter-individual variability. Furthermore, abnormal methylation of the aromatase promoter may contribute to aromatase overexpression in breast cancer.

Citations

Oct 5, 2012·Journal of Human Genetics·Edward A Ruiz-Narváez
Feb 18, 2014·Endocrine-related Cancer·Kevin C KnowerColin D Clyne
Jul 21, 2011·Journal of Osteoporosis·Daniela MerlottiRanuccio Nuti
Feb 13, 2014·European Journal of Human Genetics : EJHG·Edward A Ruiz-Narváez
Aug 30, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Sarah Q ToColin D Clyne
Jul 23, 2011·Journal of Minimally Invasive Gynecology·José Garza-LealJames E Coad
Mar 10, 2010·Molecular and Cellular Endocrinology·Kevin C KnowerColin D Clyne
Feb 17, 2010·Steroids·Daniel B Martinez-Arguelles, Vassilios Papadopoulos
Jul 11, 2008·Cancer Letters·Dong ChenSerdar E Bulun
Jan 24, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Kevin C KnowerColin D Clyne
Jan 1, 2012·Biology·Jesús Delgado-Calle, José A Riancho
May 10, 2018·Journal of the American Heart Association·Yoshimichi TakedaYoshiyu Takeda
Dec 24, 2019·Annals of the New York Academy of Sciences·John R BrachtDeborah J Clegg
Dec 11, 2020·Molecular Autism·Asad Amanat AliDarryl Walter Eyles

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.