Forger Nancy G
Neuroscience Institute, Georgia State University, Atlanta, GA 30307, USA
Philos Trans R Soc Lond B Biol Sci. 2016 Feb 19;371(1688):20150114. doi: 10.1098/rstb.2015.0114. Epub 2016 Feb 1.
Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.
仅凭间接证据就表明，大脑中性别差异的建立和维持依赖于染色质结构的表观遗传修饰。最近从两类研究中获得了更直接的证据：一类是操纵特定的表观遗传机制，另一类是研究特定表观遗传标记在全基因组中的分布。组蛋白乙酰化或DNA甲基化的操纵会破坏啮齿动物中几种神经性别差异的发育。然而，综合来看，证据表明大脑和行为的男性化或女性化发育不太可能有一个简单的模式；相反，潜在的表观遗传机制可能因脑区而异，甚至因区域内的因变量而异。与大脑性别差异相关的全基因组研究直到最近才被报道，但表明即使在两性基因表达没有差异的情况下，男性和女性可能使用不同的表观遗传修饰组合来控制基因表达。最后，讨论了近期的研究发现，这些发现可能会指导未来关于表观遗传机制在大脑和行为性别分化中作用的研究。
