MeCP2 phosphorylation in the brain: from transcription to behavior

被引:17
作者
Damen, Daniela [1 ]
Heumann, Rolf [1 ]
机构
[1] Ruhr Univ Bochum, D-44780 Bochum, Germany
关键词
DNA methylation; intellectual disability; protein phosphorylation; Rett syndrome; X-linked neurologic disorder; SEVERE MENTAL-RETARDATION; CPG-BINDING PROTEIN-2; RETT-SYNDROME; METHYL-CPG; DUPLICATION SYNDROME; GENE-EXPRESSION; MOUSE MODEL; MILD OVEREXPRESSION; DIAGNOSTIC-CRITERIA; BDNF TRANSCRIPTION;
D O I
10.1515/hsz-2013-0193
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Methyl-CpG binding protein 2 (MeCP2), a nuclear protein highly expressed in neurons, was identified because of its ability to bind methylated DNA. In association with the transcriptional corepressor proteins Sin3a and histone deacetylases, it represses gene transcription. However, it has since become clear that MeCP2 is a multifunctional protein involved not only in transcriptional silencing but also in transcriptional activation, chromatin remodeling, and RNA splicing. Especially, its involvement in the X-linked neurologic disorder Rett syndrome emphasizes the importance of MeCP2 for normal development and maturation of the central nervous system. A number of animal models with complete or partial lack of MeCP2 functions have been generated to correlate the clinical phenotype of Rett syndrome, and studies involving different mutations of MeCP2 have shown similar effects. Animal model studies have further demonstrated that even the loss of a specific phosphorylation site of MeCP2 (S80, S421, and S424) disturbs normal maturation of the mammalian brain. This review covers recent findings regarding MeCP2 functions and its regulation by posttranslational modification, particularly MeCP2 phosphorylation and its effects on mammalian brain maturation, learning, and plasticity.
引用
收藏
页码:1595 / 1605
页数:11
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