Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3113-8. doi: 10.1073/pnas.1218126110. Epub 2013 Jan 28.
Dynamic epigenetic modifications play a key role in mediating the expression of genes required for neuronal development. We previously identified nitric oxide (NO) as a signaling molecule that mediates S-nitrosylation of histone deacetylase 2 (HDAC2) and epigenetic changes in neurons. Here, we show that HDAC2 nitrosylation regulates neuronal radial migration during cortical development. Bead-array analysis performed in the developing cortex revealed that brahma (Brm), a subunit of the ATP-dependent chromatin-remodeling complex BRG/brahma-associated factor, is one of the genes regulated by S-nitrosylation of HDAC2. In the cortex, expression of a mutant form of HDAC2 that cannot be nitrosylated dramatically inhibits Brm expression. Our study identifies NO and HDAC2 nitrosylation as part of a signaling pathway that regulates cortical development and the expression of Brm in neurons.
动态表观遗传修饰在介导神经元发育所需基因的表达中起着关键作用。我们之前发现一氧化氮 (NO) 是一种信号分子，可介导组蛋白去乙酰化酶 2 (HDAC2) 的 S-亚硝基化和神经元中的表观遗传变化。在这里，我们表明 HDAC2 的亚硝基化调节皮质发育过程中的神经元放射状迁移。在发育中的皮质中进行的珠子阵列分析表明，Brahma (Brm)，一种 ATP 依赖性染色质重塑复合物 BRG/ brahma 相关因子的亚基，是受 HDAC2 亚硝基化调节的基因之一。在皮质中，不能被亚硝基化的突变型 HDAC2 形式的表达显著抑制 Brm 的表达。我们的研究将 NO 和 HDAC2 亚硝基化确定为调节皮质发育和神经元中 Brm 表达的信号通路的一部分。
