Maintaining the proper development of the female brain involves methylation-dependent silencing of key male-associated genes, finds a rodent study published this week in Nature Neuroscience. These results provide insight into the mechanisms controlling the origin and specification of mammalian sex differences.
Certain regions of the brain exhibit very different gene expression and neuronal connectivity in females and males. During mammalian fetal development, exposure to testis-derived hormones induces male patterning in the brain, which includes expression of a number of male associated genes. How these genes are expressedin males and silenced in females is unclear.
Looking in the preoptic area, a brain region that regulates certain aspects of mating behavior in rodents, Bridget Nugent and colleagues now report that DNA methylation, a process known to alter gene expression, of male-associated genes is increased in the female rat brain during a specific developmental ‘critical period’. In addition, they find that male hormones reduce the activity of DNA methyltransferase (Dnmt), the enzyme that adds methyl groups to DNA. When the authors inhibited the activity of Dnmt in female rats during brain development, the animals exhibited male-like gene expression patterns and sexual behavior.