Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta

نویسندگان

  • Ellane R. Cleys
  • Jennifer L. Halleran
  • Vanessa A. Enriquez
  • Juliano C. da Silveira
  • Rachel C. West
  • Quinton A. Winger
  • Russell V. Anthony
  • Jason E. Bruemmer
  • Colin M. Clay
  • Gerrit J. Bouma
چکیده

Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR). Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs) to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE) in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

KDM4/JMJD2 histone demethylases: epigenetic regulators in cancer cells.

Lysine methylation is one of the most prominent histone posttranslational modifications that regulate chromatin structure. Changes in histone lysine methylation status have been observed during cancer formation, which is thought to be a consequence of the dysregulation of histone lysine methyltransferases or the opposing demethylases. KDM4/JMJD2 proteins are demethylases that target histone H3 ...

متن کامل

Developmental roles of the histone lysine demethylases.

Since the discovery of the first histone lysine demethylase in 2004, two protein families with numerous members have been identified that demethylate various histone lysine residues. Initial studies of the histone lysine demethylases focused on their in vitro enzymatic activity but, more recently, model organisms have been used to examine the roles of these enzymes in vivo. Here, we review rece...

متن کامل

JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer.

Histone methylation is a dynamic process that participates in a diverse array of cellular processes and has been found to associate with cancer. Recently, several histone demethylases have been identified that catalyze the removal of methylation from histone H3 lysine residues. Through bioinformatic and biochemical analysis, we identified JARID1B as a H3K4 demethylase. Overexpression of JARID1B...

متن کامل

Hypoxia enhances the expression of prostate-specific antigen by modifying the quantity and catalytic activity of Jumonji C domain-containing histone demethylases.

Oxygen concentration in prostate cancer tissue is significantly low, i.e. ~0.3% O2. This study showed that pathological hypoxia (<0.5% O2) increased the expression of androgen receptor (AR) target genes such as prostate-specific antigen (PSA) and kallikrein-related peptidase 2 in LNCaP human prostate cancer cells by modifying the quantity and activity of related Jumonji C domain-containing hist...

متن کامل

Investigation of Histone Lysine-Specific Demethylase 5D (KDM5D) Isoform Expression in Prostate Cancer Cell Lines: a System Approach

Background: It is now well-demonstrated that histone demethylases play an important role in developmental controls, cell-fate decisions, and a variety of diseases such as cancer. Lysine-specific demethylase 5D (KDM5D) is a male-specific histone demethylase that specifically demethylates di- and tri-methyl H3K4 at the start site of active genes. In this light, the aim of this study was to invest...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 10  شماره 

صفحات  -

تاریخ انتشار 2015