DNA 甲基化和去甲基化塑造神经化学表型的性别分化。
DNA methylation and demethylation shape sexual differentiation of neurochemical phenotype.
机构信息
Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA, USA.
Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
出版信息
Horm Behav. 2023 May;151:105349. doi: 10.1016/j.yhbeh.2023.105349. Epub 2023 Mar 30.
Some of the best-studied neural sex differences depend on differential cell death in males and females, but other sex differences persist even if cell death is prevented. These include sex differences in neurochemical phenotype (i.e., stable patterns of gene expression). Work in our laboratory over the last several years has tested the hypothesis that sex differences in DNA methylation early in life underlie sexual differentiation of neuronal phenotype. We have shown that 1) expression of enzymes that place or remove DNA methylation marks is greatest during the first week of life in the mouse brain and overlaps with the perinatal critical period of sexual differentiation; 2) a transient inhibition of DNA methylation during neonatal life abolishes several sex differences in cell phenotype in the mouse hypothalamus; 3) both DNA methylation and de-methylation contribute to the development of neural sex differences; and 4) the effects of DNA methylation and de-methylation are brain region- and cell type-specific.
一些研究最为深入的神经性别差异取决于雄性和雌性细胞死亡的差异，但即使阻止细胞死亡，其他性别差异仍会持续存在。这些差异包括神经化学表型（即基因表达的稳定模式）方面的性别差异。我们实验室在过去几年中的工作检验了这样一个假设，即生命早期 DNA 甲基化的性别差异是神经元表型性别分化的基础。我们已经表明：1）在老鼠大脑中，放置或去除 DNA 甲基化标记的酶的表达在生命的第一周最大，与性分化的围产期关键期重叠；2）在新生儿期短暂抑制 DNA 甲基化会消除老鼠下丘脑细胞表型中的几个性别差异；3）DNA 甲基化和去甲基化都有助于神经性别差异的发展；4）DNA 甲基化和去甲基化的影响具有脑区和细胞类型特异性。
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