Epigenetic organization of brain sex differences and juvenile social play behavior

Abstract

The study of epigenetic mechanisms is important for elucidating how gene-by-environment interactions can have lasting outcomes on brain function and behavior. In general, studies of epigenetic processes mainly focus on the methylation status of DNA. While methylation of DNA alone can interfere with gene transcription, it is the binding of methyl-CpG binding proteins to methylated DNA, and subsequent recruitment of nuclear corepressors and histone deacetylases, that results in more efficient gene repression. In this review, we will discuss sex differences in DNA methylation patterns, methyl binding proteins, and corepressor proteins that contribute to lasting differences in brain and juvenile behavior. Specifically, we will discuss new data on sex differences in ERα DNA promoter methylation patterns, and the role of MeCP2 and the nuclear corepressor, NCoR, on the organization of juvenile social play behavior.

Figure 1

Schematic of epigenomic repression. A) Active transcriptional state. B) Methylation of DNA occurs when a methyl group attaches to a cytosine within a 5′-CpN-3′ dinucleotide site through an enzymatic reaction that is catalyzed by DNMTs. C) Methyl-CpG-binding proteins bind to methylated DNA, and D) increase the interactions of chromatin remodeling co-repressor complexes with DNA and histones, resulting in gene repression. Abbreviations: AC, acetyl group; DNMTs, DNA cytosine-5-methyltransferases; HDACs, histones deacetylases.

Figure 2

Early experiences (i.e., internal and external cues) alter DNA methylation status in developing brain. Differences in methylation status may contribute to typical and atypical brain function and behavior.