The epigenetics of sex differences in the brain.
The epigenetics of sex differences in the brain.
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大脑性别差异的表观遗传学。
DOI：
10.1523/jneurosci.3331-09.2009
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发表时间：
2009-10-14
影响因子：
5.3
通讯作者：
Wilson, Melinda E.
中科院分区：
文献类型：
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作者：
McCarthy, Margaret M.;Auger, Anthony P.;Bale, Tracy L.;De Vries, Geert J.;Dunn, Gregory A.;Forger, Nancy G.;Murray, Elaine K.;Nugent, Bridget M.;Schwarz, Jaclyn M.;Wilson, Melinda E.
神经系统的表观遗传变化正在成为早期生活经历、激素暴露、创伤和损伤或学习和记忆引起的持久影响的一个关键组成部分。大脑中的性别差异在很大程度上是由围产期敏感期的类固醇激素暴露决定的，这会改变整个生命周期中随后的激素和非激素反应。类固醇受体是核受体转录因子超家族的成员，并募集具有与表观遗传变化（如乙酰化和甲基化）相关的酶活性的多种蛋白质。因此，类固醇激素是独一无二的，它对发育中的神经系统产生表观遗传效应，决定了成年人大脑和行为的性别差异。雌激素和孕激素受体基因启动子甲基化模式的性别差异在新生儿中很明显，在成人中也存在，但模式不同。也报道了甲基结合蛋白和类固醇受体共调节蛋白对损伤的反应的变化。许多类固醇引起的表观遗传变化是机会性的，并限于一个单一的寿命，但新的证据表明，内分泌干扰化合物可以发挥多代的影响。同样，母亲的饮食也会引起跨代效应，但这种影响是性别特异性的。性别差异的表观遗传学研究还处于早期阶段，需要在了解控制乙酰化和甲基化的酶的激素调节、共调节蛋白、瞬时与稳定的DNA甲基化模式以及表观基因组的性别差异方面取得进展，以充分了解大脑和行为的性别差异。
Epigenetic changes in the nervous system are emerging as a critical component of enduring effects induced by early life experience, hormonal exposure, trauma and injury or learning and memory. Sex differences in the brain are largely determined by steroid hormone exposure during a perinatal sensitive period that alters subsequent hormonal and non-hormonal responses throughout the life span. Steroid receptors are members of a nuclear receptor transcription factor superfamily and recruit multiple proteins that possess enzymatic activity relevant to epigenetic changes such as acetylation and methylation. Thus steroid hormones are uniquely poised to exert epigenetic effects on the developing nervous system to dictate adult sex differences in brain and behavior. Sex differences in the methylation pattern in the promoter of estrogen and progesterone receptor genes are evident in newborns and persist in adults but with a different pattern. Changes in response to injury and in methyl binding proteins and steroid receptor coregulatory proteins are also reported. Many steroid-induced epigenetic changes are opportunistic and restricted to a single lifespan but new evidence suggests endocrine disrupting compounds can exert multigenerational effects. Similarly, maternal diet also induces transgenerational effects but the impact is sex specific. The study of epigenetics of sex differences is in its earliest stages, with needed advances in understanding of the hormonal regulation of enzymes controlling acetylation and methylation, coregulatory proteins, transient versus stable DNA methylation patterns and sex differences across the epigenome in order to fully understand sex differences in brain and behavior.