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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.
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