Urdinguio Rocio G, Pino Irene, Ropero Santiago, Fraga Mario F, Esteller Manel
Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Epigenetics. 2007 Jan-Mar;2(1):11-4. doi: 10.4161/epi.2.1.3698. Epub 2006 Dec 12.
Rett syndrome (RTT) is a complex neurodevelopmental disorder that has been associated with mutations of methyl-CpG binding protein 2 (MeCP2). MeCP2 acts as a transcriptional repressor and binds to histone modifier proteins, which prompted us to wonder whether MeCP2 disruption affects global histone modification patterns. Taking a two-fold approach of using high-performance capillary electrophoresis (HPCE) and western blot, we analyzed the acetylation and methylation status of histones H3 and H4 in a mouse model of RTT where the MeCP2 locus is genetically disrupted. The comparison of cortex, midbrain and cerebellum in wild-type and MeCP2-knock out mice did not reveal any significant difference in the global H3 and H4 histone modification patterns. Our results suggest that MeCP2 deficiency involves local and gene-specific chromatin changes rather than massive histone modification changes.
雷特综合征（RTT）是一种复杂的神经发育障碍，与甲基-CpG结合蛋白2（MeCP2）的突变有关。MeCP2作为一种转录抑制因子，与组蛋白修饰蛋白结合，这促使我们思考MeCP2的破坏是否会影响整体组蛋白修饰模式。我们采用高效毛细管电泳（HPCE）和蛋白质印迹的双重方法，分析了MeCP2基因座发生基因破坏的雷特综合征小鼠模型中组蛋白H3和H4的乙酰化和甲基化状态。对野生型和MeCP2基因敲除小鼠的皮质、中脑和小脑进行比较，未发现整体H3和H4组蛋白修饰模式有任何显著差异。我们的结果表明，MeCP2缺乏涉及局部和基因特异性的染色质变化，而非大规模的组蛋白修饰变化。
