Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation
Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation
复制标题
DOI：
10.1073/pnas.0608056104
复制
发表时间：
2007-02-20
影响因子：
11.1
通讯作者：
Bird, Adrian
中科院分区：
文献类型：
--
作者：
Nan, Xinsheng;Hou, Jianghui;Bird, Adrian
人类甲基CpG结合蛋白基因MECP 2的突变导致神经系统疾病Rett综合征和一些X连锁智力低下（XLMR）病例。我们报告MeCP 2与ATRX相互作用，ATRX是一种SW 12/SNF 2 DNA解旋酶/ATP酶，在ATRX综合征（α-地中海贫血/精神发育迟滞，X连锁）中突变。MeCP 2可以招募解旋酶域ATRX异染色质灶在活的小鼠细胞中的DNA甲基化依赖性的方式。此外，ATRX定位在Mecp 2缺失小鼠的神经元中被破坏。导致Rett综合征或X连锁精神发育迟滞的MeCP 2甲基化DNA结合结构域内的点突变抑制其与ATRX的体外相互作用及其体内定位，而不影响甲基-CpG结合。我们建议，中断的MeCP 2-ATRX相互作用导致病理变化，有助于精神发育迟滞。
Mutations in the human methyl-CpG-binding protein gene MECP2 cause the neurological disorder Rett syndrome and some cases of X-linked mental retardation (XLMR). We report that MeCP2 interacts with ATRX, a SW12/SNF2 DNA helicase/ATPase that is mutated in ATRX syndrome (alpha-thalassemia/mental retardation, X-linked). MeCP2 can recruit the helicase domain of ATRX to heterochromatic foci in living mouse cells in a DNA methylation-dependent manner. Also, ATRX localization is disrupted in neurons of Mecp2-null mice. Point mutations within the methylated DNA-binding domain of MeCP2 that cause Rett syndrome or X-linked mental retardation inhibit its interaction with ATRX in vitro and its localization in vivo without affecting methyl-CpG binding. We propose that disruption of the MeCP2-ATRX interaction leads to pathological changes that contribute to mental retardation.