THE McCARTHY LAB
Investigating the Sex Differences in the Developing Brain
Epigenetics of Sex Differences in the Brain
When we think about enduring early life hormone exposure effects, we think epigenetics. Epigenetics refers to modifications to DNA or associated histones that do not change nucleotide sequences but have long term impacts on gene expression. Epigenetic modifications include DNA methylation, histone modifications (acetylation, methylation and phosphorylation) and chromatin remodeling. Steroids directly act on DNA by binding to nuclear transcription factors, establishing connections for epigenetics and sex differentiation of the brain.
Recent investigations from our lab provide evidence that:
DNA methylation prevents masculinization and is essential to both the initiation and maintenance of sexual differentiation in the mPOA.
Female rats show higher levels of DNA methyltranfersase (DNMT) activity than males. The DNMT activity of females treated with a masculinizing dose of steroids during the first week of life is reduced to male levels.
Histone deacetylation is required for masculinization of the rat brain