CDKL5 is a brain MeCP2 target gene regulated by DNA methylation

被引:80
作者
Carouge, Delphine
Host, Lionel
Aunis, Dominique
Zwiller, Jean [2 ]
Anglard, Patrick [1 ,2 ]
机构
[1] Univ Strasbourg, Unite INSERM U575, Ctr Neurochim, INSERM,U575, F-67084 Strasbourg, France
[2] CNRS, FRE 3289, LINC, F-67000 Strasbourg, France
关键词
Rett syndrome; Neurodevelopmental disorders; Drug of abuse; Epigenetics; DNA methylation; Chromatin remodeling; MeCP2; RETT-SYNDROME; EPIGENETIC REGULATION; CHROMATIN-STRUCTURE; INFANTILE SPASMS; MATERNAL-CARE; CPG-ISLANDS; MOUSE MODEL; EXPRESSION; MUTATIONS; PROMOTER;
D O I
10.1016/j.nbd.2010.02.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rett syndrome and its "early-onset seizure" variant are severe neurodevelopmental disorders associated with mutations within the MECP2 and the CDKL5 genes. Antidepressants and drugs of abuse induce the expression of the epigenetic factor MeCP2, thereby influencing chromatin remodeling. We show that increased MeCP2 levels resulted in the repression of Cdk15 in rat brain structures in response to cocaine, as well as in cells exposed to serotonin, or overexpressing MeCP2. In contrast, Cdk15 was induced by siRNA-mediated knockdown of Mecp2 and by DNA-methyltransferase inhibitors, demonstrating its regulation by MeCP2 and by DNA methylation. Cdk15 gene methylation and its methylation-dependent binding to MeCP2 were increased in the striatum of cocaine-treated rats. Our data demonstrate that Cdk15 is a MeCP2-repressed target gene providing a link between genes the mutation of which generates overlapping symptoms. They highlight DNA methylation changes as a potential mechanism participating in the long-term plasticity triggered by pharmacological agents. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:414 / 424
页数:11
相关论文
共 62 条
[1]   Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 [J].
Amir, RE ;
Van den Veyver, IB ;
Wan, M ;
Tran, CQ ;
Francke, U ;
Zoghbi, HY .
NATURE GENETICS, 1999, 23 (02) :185-188
[2]   Early-onset seizure variant of Rett syndrome: Definition of the clinical diagnostic criteria [J].
Artuso, R. ;
Mencarelli, M. A. ;
Polli, R. ;
Sartori, S. ;
Ariani, F. ;
Pollazzon, M. ;
Marozza, A. ;
Cilio, M. R. ;
Specchio, N. ;
Vigevano, F. ;
Vecchi, M. ;
Boniver, C. ;
Dalla Bernardina, B. ;
Parmeggiani, A. ;
Buoni, S. ;
Hayek, G. ;
Mari, F. ;
Renieri, A. ;
Murgia, A. .
BRAIN & DEVELOPMENT, 2010, 32 (01) :17-24
[3]   Key clinical features to identify girls with CDKL5 mutations [J].
Bahi-Buisson, Nadia ;
Nectoux, Juliette ;
Rosas-Vargas, Haydee ;
Milh, Mathieu ;
Boddaert, Nathalie ;
Girard, Benoit ;
Cances, Claude ;
Ville, Dorothee ;
Afenjar, Alexandra ;
Rio, Marlene ;
Heron, Delphine ;
Morel, Marie Ange N'Guyen ;
Arzimanoglou, Alexis ;
Philippe, Christophe ;
Jonveaux, Philippe ;
Chelly, Jamel ;
Bienvenu, Thierry .
BRAIN, 2008, 131 :2647-2661
[4]   Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation [J].
Bertani, Ilaria ;
Rusconi, Laura ;
Bolognese, Fabrizio ;
Forlani, Greta ;
Conca, Barbara ;
De Monte, Lucia ;
Badaracco, Gianfranco ;
Landsberger, Nicoletta ;
Kilstrup-Nielsen, Charlotte .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (42) :32048-32056
[5]   DNA methylation patterns and epigenetic memory [J].
Bird, A .
GENES & DEVELOPMENT, 2002, 16 (01) :6-21
[6]   Molecular biology - Methylation talk between histones and DNA [J].
Bird, A .
SCIENCE, 2001, 294 (5549) :2113-2115
[7]   Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J].
Cameron, EE ;
Bachman, KE ;
Myöhänen, S ;
Herman, JG ;
Baylin, SB .
NATURE GENETICS, 1999, 21 (01) :103-107
[8]   Expression of the methyl-CpG-binding protein MeCP2 in rat brain. An ontogenetic study [J].
Cassel, S ;
Revel, MO ;
Kelche, C ;
Zwiller, J .
NEUROBIOLOGY OF DISEASE, 2004, 15 (02) :206-211
[9]   Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain [J].
Cassel, Suzanne ;
Carouge, Delphine ;
Gensburger, Claire ;
Anglard, Patrick ;
Burgun, Claude ;
Dietrich, Jean-Bernard ;
Aunis, Dominique ;
Zwiller, Jean .
MOLECULAR PHARMACOLOGY, 2006, 70 (02) :487-492
[10]   The story of Rett syndrome: From clinic to neurobiology [J].
Chahrour, Maria ;
Zoghbi, Huda Y. .
NEURON, 2007, 56 (03) :422-437