Masahiro Uesaka and Takuya Imamura
During mammalian development, androgen circulates throughout the body and masculinizes several tissues through endocrinological pathways by binding androgen receptor (AR). At the onset of brain masculinization/defeminization, the androgen-AR system functions in a region-specific manner and, even in adulthood, this system affects the transcription of a certain set of genes. The androgen-AR system, together with several coregulators such as histone modifiers, epigenetically regulates many kinds of genes to express the phenotype of a cell according to the cell’s own androgensensitivity as well as the dose of androgen to which it is exposed. Long-range DNA-protein interactions via chromatin looping structures also set up epigenetic regulatory mechanisms that affect the androgen responsiveness. Importantly, the androgen-AR system regulates the transcription of AR itself. For such autoregulation, there are a variety of ciselements within the coding sequences as well as in the regulatory region of AR, including multiple androgen response elements. We found that some of these cis-elements diverged across species: among them there are several primatespecific regions and rodent-specific regions including a short interspersed element, called B2 SINE, as shown by comparisons between primates and rodents. These data suggest that the gain and/or loss of cis-elements by deletion, insertion and mutation determines the species-specific regulation of AR transcription. Differences in the sequences of AR/Ar regulatory regions may contribute to species-specific transcription regulation in genetic and epigenetic manners. Studies focusing on the biodiversity of the AR regulatory region are important for understanding the diversity of the epigenetic setting determining the responsiveness of cells to androgen.
