Normal histone modifications on the inactive X chromosome in ICF and Rett syndrome cells: implications for methyl-CpG binding proteins
Normal histone modifications on the inactive X chromosome in ICF and Rett syndrome cells: implications for methyl-CpG binding proteins
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DOI：
10.1186/1741-7007-2-21
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发表时间：
2004-01-01
期刊：
影响因子：
5.4
通讯作者：
Hansen, R. Scott
中科院分区：
文献类型：
--
作者：
Gartler, Stanley M.;Varadarajan, Kartik R.;Hansen, R. Scott
背景：在哺乳动物中，有证据表明，甲基-CpG结合蛋白可能通过与修饰复合体结合而在组蛋白修饰中发挥重要作用，这些修饰复合体可以在甲基化DNA附近对核小体进行脱乙酰化和/或甲基化。我们通过研究正常细胞和ICF综合征(免疫缺陷、着丝粒区域不稳定和面部畸形综合征)患者X染色体上的组蛋白修饰来检验X染色体的这一想法。在正常细胞中，失活的X具有典型的沉默类型的组蛋白修饰模式，而受X失活影响的基因的CpG岛被高甲基化。然而，在ICF细胞中，由于DNA甲基转移酶(Dnmt3b)基因的突变，导致X失活的基因在失活的X上发生低甲基化。因此，如果DNA甲基化是组蛋白修饰的上游，ICF细胞中非活性X上的组蛋白不应该被修改为沉默的形式。此外，我们通过研究缺乏MeCP2功能的Rett综合征细胞，确定了特定的甲基-CpG结合蛋白MeCP2是否是非活性X组蛋白修饰模式所必需的。结果：我们在这里显示，ICF细胞中的非活性X似乎在所有CpG岛上都是低甲基化的，表现出正常的组蛋白修饰模式。此外，在没有功能性MeCP2甲基-CpG结合蛋白的RETT细胞中，非活性X也表现出正常的组蛋白修饰模式。结论：这些数据表明，DNA甲基化和相关的甲基DNA结合蛋白可能在决定哺乳动物非活性X染色体上所分析位点的组蛋白修饰模式中不起关键作用。
Background: In mammals, there is evidence suggesting that methyl-CpG binding proteins may play a significant role in histone modification through their association with modification complexes that can deacetylate and/or methylate nucleosomes in the proximity of methylated DNA. We examined this idea for the X chromosome by studying histone modifications on the X chromosome in normal cells and in cells from patients with ICF syndrome (Immune deficiency, Centromeric region instability, and Facial anomalies syndrome). In normal cells the inactive X has characteristic silencing type histone modification patterns and the CpG islands of genes subject to X inactivation are hypermethylated. In ICF cells, however, genes subject to X inactivation are hypomethylated on the inactive X due to mutations in the DNA methyltransferase (DNMT3B) genes. Therefore, if DNA methylation is upstream of histone modification, the histones on the inactive X in ICF cells should not be modified to a silent form. In addition, we determined whether a specific methyl-CpG binding protein, MeCP2, is necessary for the inactive X histone modification pattern by studying Rett syndrome cells which are deficient in MeCP2 function.Results: We show here that the inactive X in ICF cells, which appears to be hypomethylated at all CpG islands, exhibits normal histone modification patterns. In addition, in Rett cells with no functional MeCP2 methyl-CpG binding protein, the inactive X also exhibits normal histone modification patterns.Conclusions: These data suggest that DNA methylation and the associated methyl-DNA binding proteins may not play a critical role in determining histone modification patterns on the mammalian inactive X chromosome at the sites analyzed.