methyl cpg binding protein 2


Summary: A DNA-binding protein that interacts with methylated CPG ISLANDS. It plays a role in repressing GENETIC TRANSCRIPTION and is frequently mutated in RETT SYNDROME.

Top Publications

  1. Dragich J, Kim Y, Arnold A, Schanen N. Differential distribution of the MeCP2 splice variants in the postnatal mouse brain. J Comp Neurol. 2007;501:526-42 pubmed
    Mutations in the gene encoding methyl CpG binding protein 2 (MeCP2) are the primary cause of the neurodevelopmental disorder Rett syndrome (RTT)...
  2. Deng V, Matagne V, Banine F, Frerking M, Ohliger P, Budden S, et al. FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice. Hum Mol Genet. 2007;16:640-50 pubmed
    ..FXYD1 is therefore a MeCP2 target gene whose de-repression may directly contribute to RTT neuronal pathogenesis. ..
  3. Smrt R, Eaves Egenes J, Barkho B, Santistevan N, Zhao C, Aimone J, et al. Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol Dis. 2007;27:77-89 pubmed
    ..Our studies suggest that MeCP2 plays a central role in neuronal maturation, which might be mediated through epigenetic control of expression pathways that are instrumental in both dendritic development and synaptogenesis. ..
  4. Gibson J, Slobedman B, K N H, Williamson S, Minchenko D, El Osta A, et al. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain. BMC Neurosci. 2010;11:53 pubmed publisher
    ..The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected...
  5. Degano A, Pasterkamp R, Ronnett G. MeCP2 deficiency disrupts axonal guidance, fasciculation, and targeting by altering Semaphorin 3F function. Mol Cell Neurosci. 2009;42:243-54 pubmed publisher
    ..These findings have broad implications for the role of MECP2 in neurodevelopment and RTT, given the critical role of the semaphorins in the formation of neural circuits. ..
  6. Lugtenberg D, Kleefstra T, Oudakker A, Nillesen W, Yntema H, Tzschach A, et al. Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum Genet. 2009;17:444-53 pubmed publisher
    ..We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms. ..
  7. Ben Shachar S, Chahrour M, Thaller C, Shaw C, Zoghbi H. Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum Mol Genet. 2009;18:2431-42 pubmed publisher
    ..Further delineation of the expression pattern of MeCP2 target genes throughout the brain might identify subsets of genes that are more amenable to manipulation, and can thus be used to modulate some of the disease phenotypes. ..
  8. Dani V, Nelson S. Intact long-term potentiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome. J Neurosci. 2009;29:11263-70 pubmed publisher
    ..However, fewer connections were found in Mecp2-null mice and individual connections were weaker. These data suggest that loss of MeCP2 function reduces excitatory synaptic connectivity and that this precedes deficits in plasticity. ..
  9. Larimore J, Chapleau C, Kudo S, Theibert A, Percy A, Pozzo Miller L. Bdnf overexpression in hippocampal neurons prevents dendritic atrophy caused by Rett-associated MECP2 mutations. Neurobiol Dis. 2009;34:199-211 pubmed publisher
    ..Our results demonstrate that MeCP2 plays varied roles in dendritic and axonal development during neuronal terminal differentiation, and that some of these effects are mediated by autocrine actions of BDNF. ..

More Information


  1. Zhang Z, Zak J, Liu H. MeCP2 is required for normal development of GABAergic circuits in the thalamus. J Neurophysiol. 2010;103:2470-81 pubmed publisher
    ..Our findings suggest that MeCP2 differentially regulates the development of GABAergic synapses in excitatory and inhibitory neurons in the thalamus...
  2. Skene P, Illingworth R, Webb S, Kerr A, James K, Turner D, et al. Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell. 2010;37:457-68 pubmed publisher
    ..Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner. ..
  3. Chapleau C, Calfa G, Lane M, Albertson A, Larimore J, Kudo S, et al. Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol Dis. 2009;35:219-33 pubmed publisher
  4. Hotta A, Cheung A, Farra N, Vijayaragavan K, Séguin C, Draper J, et al. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat Methods. 2009;6:370-6 pubmed publisher
    ..Finally, we used EOS selection to establish Rett syndrome-specific mouse and human iPS cell lines with known mutations in MECP2. ..
  5. Maezawa I, Swanberg S, Harvey D, LaSalle J, Jin L. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci. 2009;29:5051-61 pubmed publisher
    ..Our results suggest that astrocytes are viable therapeutic targets for RTT and perhaps regressive forms of autism. ..
  6. Adachi M, Autry A, Covington H, Monteggia L. MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome. J Neurosci. 2009;29:4218-27 pubmed publisher
    ..These results suggest a key role for Mecp2 as a transcriptional repressor in the BLA in mediating behavioral features of RTT. ..
  7. Tao J, Hu K, Chang Q, Wu H, Sherman N, Martinowich K, et al. Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci U S A. 2009;106:4882-7 pubmed publisher
    ..We postulate that phosphorylation of MeCP2 modulates its dynamic function in neurons transiting between resting and active states within neural circuits that underlie behaviors. ..
  8. Monteggia L, Kavalali E. Rett syndrome and the impact of MeCP2 associated transcriptional mechanisms on neurotransmission. Biol Psychiatry. 2009;65:204-10 pubmed publisher
    ..In addition, this work will also help delineate a key pathway that regulates properties of neurotransmission in the central nervous system that may underlie additional neuropsychiatric disorders. ..
  9. Maliszewska Cyna E, Bawa D, Eubanks J. Diminished prevalence but preserved synaptic distribution of N-methyl-D-aspartate receptor subunits in the methyl CpG binding protein 2(MeCP2)-null mouse brain. Neuroscience. 2010;168:624-32 pubmed publisher
    ..of NMDA receptor subunits within crude synaptic membranes derived from the brains of mice lacking methyl CpG binding protein 2 (MeCP2)...
  10. Jin J, Bao X, Wang H, Pan H, Zhang Y, Wu X. RNAi-induced down-regulation of Mecp2 expression in the rat brain. Int J Dev Neurosci. 2008;26:457-65 pubmed publisher
    ..Bdnf mRNA expression decreased in the hippocampus, supporting the hypothesis that Bdnf may be a target gene of MeCP2 in the CNS. ..
  11. Buoni S, Zannolli R, De Felice C, De Nicola A, Guerri V, Guerra B, et al. EEG features and epilepsy in MECP2-mutated patients with the Zappella variant of Rett syndrome. Clin Neurophysiol. 2010;121:652-7 pubmed publisher
    ..These results could offer support in the practical management of patients and family counseling. ..
  12. Bartsch O, Gebauer K, Lechno S, Van Esch H, Froyen G, Bonin M, et al. Four unrelated patients with Lubs X-linked mental retardation syndrome and different Xq28 duplications. Am J Med Genet A. 2010;152A:305-12 pubmed publisher
    ..Because injection of botulinum toxin (BT-A; Botox) proved to be extremely helpful for patient 1, we recommend consideration of Botox treatment in other patients with MRXSL and severe joint contractures. ..
  13. Campos M, Churchman S, Santos Rebouças C, Ponchel F, Pimentel M. High frequency of nonrecurrent MECP2 duplications among Brazilian males with mental retardation. J Mol Neurosci. 2010;41:105-9 pubmed publisher
  14. De Felice C, Guazzi G, Rossi M, Ciccoli L, Signorini C, Leoncini S, et al. Unrecognized lung disease in classic Rett syndrome: a physiologic and high-resolution CT imaging study. Chest. 2010;138:386-92 pubmed publisher
    ..Further research is needed to clarify the epidemiologic characteristics and the pathogenesis of these previously unrecognized pulmonary abnormalities. ..
  15. Lotan M, Merrick J, Kandel I, Morad M. Aging in persons with Rett syndrome: an updated review. ScientificWorldJournal. 2010;10:778-87 pubmed publisher
  16. Bond A, Vangompel M, Sametsky E, Clark M, Savage J, Disterhoft J, et al. Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nat Neurosci. 2009;12:1020-7 pubmed publisher
    ..These results suggest that noncoding RNA-dependent balanced gene regulation in embryonic brain is critical for proper formation of GABA-dependent neuronal circuitry in adult brain. ..
  17. Buschdorf J, Strätling W. A WW domain binding region in methyl-CpG-binding protein MeCP2: impact on Rett syndrome. J Mol Med (Berl). 2004;82:135-43 pubmed
    ..Furthermore, a short C-terminal truncation and an internal deletion, both causing mild to moderate mental retardation in males, were associated with weak or loss of WW domain binding activity. ..
  18. Glaze D, Percy A, Motil K, Lane J, Isaacs J, Schultz R, et al. A study of the treatment of Rett syndrome with folate and betaine. J Child Neurol. 2009;24:551-6 pubmed publisher
    ..This study should inform future treatment trials regarding balancing participants with specific mutations and comparable severity to minimize selection bias. ..
  19. Khajuria R, Sapra S, Ghosh M, Gupta N, Gulati S, Kalra V, et al. Rapid detection of deletions in hotspot C-terminal segment region of MECP2 by routine PCR method: report of two classical Rett syndrome patients of Indian origin. Genet Test Mol Biomarkers. 2009;13:277-80 pubmed publisher
    ..Sporadic or de novo mutations of the methyl CpG binding protein 2 (MECP2) gene have been reported in 70-90% of affected girls...
  20. Baris I, Battaloglu E. A multiplexed ARMS-PCR approach for the detection of common MECP2 mutations. Genet Test Mol Biomarkers. 2009;13:19-22 pubmed publisher
    ..The assay can be carried out efficiently in a standard molecular genetics laboratory and suitable as a preliminary screen for all patients with RTT diagnosis. ..
  21. Saunders C, Friez M, Patterson M, Nzabi M, Zhao W, Bi C. Allele drop-out in the MECP2 gene due to G-quadruplex and i-motif sequences when using polymerase chain reaction-based diagnosis for Rett syndrome. Genet Test Mol Biomarkers. 2010;14:241-7 pubmed publisher
    ..We identify factors in both the polymerase chain reaction amplification and the sequencing steps that help overcome ADO. ..
  22. De Felice C, Ciccoli L, Leoncini S, Signorini C, Rossi M, Vannuccini L, et al. Systemic oxidative stress in classic Rett syndrome. Free Radic Biol Med. 2009;47:440-8 pubmed publisher
    ..These data identify hypoxia-induced oxidative stress as a key factor in the pathogenesis of classic RS and suggest new therapeutic approaches based on oxidative stress modulation...
  23. D Cruz J, Wu C, Zahid T, El Hayek Y, Zhang L, Eubanks J. Alterations of cortical and hippocampal EEG activity in MeCP2-deficient mice. Neurobiol Dis. 2010;38:8-16 pubmed publisher
    ..Collectively, these findings indicate that a deficiency in MeCP2 function in mice leads to alterations in EEG activity with similarities to what has been observed clinically in Rett syndrome patients. ..
  24. Zhang B, Deng D. [Effects of methylation status of CpG islands on results of luciferase reporter assay]. Zhonghua Yu Fang Yi Xue Za Zhi. 2009;43:601-6 pubmed
    ..915, P values were 0.010 and 0.003). The methylation status of CpG island of the target gene in the tested cell lines affects the promoter activity in Reporter Assay significantly. The most active one may be the most suppressive one. ..
  25. Cohen S, Greenberg M. Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Annu Rev Cell Dev Biol. 2008;24:183-209 pubmed publisher
  26. Kudo S, Nomura Y, Segawa M, Fujita N, Nakao M, Dragich J, et al. Functional analyses of MeCP2 mutations associated with Rett syndrome using transient expression systems. Brain Dev. 2001;23 Suppl 1:S165-73 pubmed
    ..Thus, these functional assays are useful to evaluate the consequences of mutation in the methyl-CpG-binding domain of MeCP2 and provide an insight into the relationship between the genotype and the severity of Rett syndrome. ..
  27. Webb R, Wren J, Jeffries M, Kelly J, Kaufman K, Tang Y, et al. Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus. Arthritis Rheum. 2009;60:1076-84 pubmed publisher
    ..Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients. ..
  28. Wang Z, Udeshi N, O Malley M, Shabanowitz J, Hunt D, Hart G. Enrichment and site mapping of O-linked N-acetylglucosamine by a combination of chemical/enzymatic tagging, photochemical cleavage, and electron transfer dissociation mass spectrometry. Mol Cell Proteomics. 2010;9:153-60 pubmed publisher
    ..Using this strategy, eight O-GlcNAc sites were mapped from a tau-enriched sample from rat brain. Sites of GlcNAcylation were characterized on important neuronal proteins such as tau, synucleins, and methyl CpG-binding protein 2. ..
  29. Kifayathullah L, Arunachalam J, Bodda C, Agbemenyah H, Laccone F, Mannan A. MeCP2 mutant protein is expressed in astrocytes as well as in neurons and localizes in the nucleus. Cytogenet Genome Res. 2010;129:290-7 pubmed publisher
    ..Our data showing expression of MeCP2(270_EGFP) in transgenic mice astrocytes further reinforce the recent findings concerning the expression of MeCP2 in the glial cells. ..
  30. Mencarelli M, Spanhol Rosseto A, Artuso R, Rondinella D, De Filippis R, Bahi Buisson N, et al. Novel FOXG1 mutations associated with the congenital variant of Rett syndrome. J Med Genet. 2010;47:49-53 pubmed publisher
    ..Scoliosis was present and severe in the older patients. Neurovegetative symptoms typical of Rett were frequently present. ..
  31. Belichenko P, Wright E, Belichenko N, Masliah E, Li H, Mobley W, et al. Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome: evidence for disruption of neuronal networks. J Comp Neurol. 2009;514:240-58 pubmed publisher
    ..Electron microscopy confirmed abnormalities in dendrites and axons and showed abnormal mitochondria. Our findings document widespread abnormalities of dendrites and axons that recapitulate those seen in RTT. ..
  32. Blardi P, de Lalla A, D Ambrogio T, Vonella G, Ceccatelli L, Auteri A, et al. Long-term plasma levels of leptin and adiponectin in Rett syndrome. Clin Endocrinol (Oxf). 2009;70:706-9 pubmed publisher
    ..Since all patients were not obese, we might hypothesize that in Rett syndrome leptin and adiponectin might participate to clinical manifestations other than weight balance. ..
  33. Zhang J, Bao X, Cao G, Jiang S, Zhu X, Lu H, et al. [Analysis of the parental origin of MECP2 mutations in patients with Rett syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:121-4 pubmed publisher
    ..The mutation types of the 3 patients with maternal origin included 2 frame shift and 1 point (C >T) mutation. In Chinese RTT patients, the MECP2 mutations are mostly of paternal origin. ..
  34. Wilson M, Westberry J. Regulation of oestrogen receptor gene expression: new insights and novel mechanisms. J Neuroendocrinol. 2009;21:238-42 pubmed publisher
    ..Data from our laboratory demonstrate that the promoters of the ERalpha gene are also methylated during development and after neuronal injury, suggesting a role of DNA methylation in regulating ER expression in the brain. ..
  35. Forlani G, Giarda E, Ala U, Di Cunto F, Salani M, Tupler R, et al. The MeCP2/YY1 interaction regulates ANT1 expression at 4q35: novel hints for Rett syndrome pathogenesis. Hum Mol Genet. 2010;19:3114-23 pubmed publisher
    ..As both ANT1 mutations and overexpression have been associated with human diseases, we consider it highly relevant to address the consequences of ANT1 deregulation in Rett syndrome. ..
  36. Downs J, Bebbington A, Jacoby P, Williams A, Ghosh S, Kaufmann W, et al. Level of purposeful hand function as a marker of clinical severity in Rett syndrome. Dev Med Child Neurol. 2010;52:817-23 pubmed publisher
    ..mean age of 14 years 10 months (SD 7 y 10 mo; range 2 y-31 y 10 mo), 110 of whom had a mutation of the methyl CpG binding protein 2 (MECP2) gene...
  37. Rio M, Malan V, Boissel S, Toutain A, Royer G, Gobin S, et al. Familial interstitial Xq27.3q28 duplication encompassing the FMR1 gene but not the MECP2 gene causes a new syndromic mental retardation condition. Eur J Hum Genet. 2010;18:285-90 pubmed publisher
    ..This family broadens the phenotypic spectrum of FMR1 anomalies in an unexpected manner, and we suggest that this condition may represent the fragile X syndrome "contre-type". ..
  38. Voituron N, Zanella S, Menuet C, Lajard A, Dutschmann M, Hilaire G. Early abnormalities of post-sigh breathing in a mouse model of Rett syndrome. Respir Physiol Neurobiol. 2010;170:173-82 pubmed publisher
  39. Roux J, Villard L. Biogenic amines in Rett syndrome: the usual suspects. Behav Genet. 2010;40:59-75 pubmed publisher
    ..Given our current knowledge and the tools available, modulating biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of Rett syndrome patients in the short term. ..
  40. Specchio N, Balestri M, Striano P, Cilio M, Nardello R, Patanè S, et al. Efficacy of levetiracetam in the treatment of drug-resistant Rett syndrome. Epilepsy Res. 2010;88:112-7 pubmed publisher
    ..Levetiracetam appeared effective in our series of drug-resistant RTT patients. All reported a reduction in seizure frequency and consequently a better quality of life. ..
  41. Cowansage K, LeDoux J, Monfils M. Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity. Curr Mol Pharmacol. 2010;3:12-29 pubmed
    ..We conclude by emphasizing the importance of characterizing BDNF signaling cascades in behaviorally-relevant networks, to identify potential drug targets for novel therapeutic interventions. ..
  42. Chao H, Chen H, Samaco R, Xue M, Chahrour M, Yoo J, et al. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature. 2010;468:263-9 pubmed publisher
    ..These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes. ..
  43. Deng J, Rodriguiz R, Hutchinson A, Kim I, Wetsel W, West A. MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nat Neurosci. 2010;13:1128-36 pubmed publisher
    ..These data reveal new roles for MeCP2 both in mesolimbocortical circuit development and in the regulation of psychostimulant-induced behaviors...
  44. Voituron N, Menuet C, Dutschmann M, Hilaire G. Physiological definition of upper airway obstructions in mouse model for Rett syndrome. Respir Physiol Neurobiol. 2010;173:146-56 pubmed publisher
    ..The observed breath-hold events in Mecp2(-/y) mice might imply disturbance of neural circuits attached to voluntary control of breathing. ..
  45. Mironov S, Skorova E, Hartelt N, Mironova L, Hasan M, Kugler S. Remodelling of the respiratory network in a mouse model of Rett syndrome depends on brain-derived neurotrophic factor regulated slow calcium buffering. J Physiol. 2009;587:2473-85 pubmed publisher
  46. Jentarra G, Olfers S, Rice S, Srivastava N, Homanics G, Blue M, et al. Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation. BMC Neurosci. 2010;11:19 pubmed publisher
  47. Matsumura S, Persson L, Wong L, Wilson A. The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains. J Virol. 2010;84:2318-30 pubmed publisher
  48. Psoni S, Sofocleous C, Traeger Synodinos J, Kitsiou Tzeli S, Kanavakis E, Fryssira Kanioura H. Phenotypic and genotypic variability in four males with MECP2 gene sequence aberrations including a novel deletion. Pediatr Res. 2010;67:551-6 pubmed publisher
    ..Patients 2 and 3 had a novel deletion (c.1140del86) inherited from their unaffected mother. MECP2 gene mutations may be considered a rare cause of MR in males although great phenotypic variation hinders genotype-phenotype correlation. ..
  49. Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis S, et al. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features. Clin Genet. 2010;78:175-80 pubmed publisher
    ..This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation. ..
  50. Harikrishnan K, Bayles R, Ciccotosto G, Maxwell S, Cappai R, Pelka G, et al. Alleviating transcriptional inhibition of the norepinephrine slc6a2 transporter gene in depolarized neurons. J Neurosci. 2010;30:1494-501 pubmed publisher
    ..These results now begin to offer a new perspective on the mechanism of Slc6a2 gene regulation. ..
  51. Sprovieri T, Conforti F, Fiumara A, Mazzei R, Ungaro C, Citrigno L, et al. A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype. Am J Med Genet A. 2009;149A:722-5 pubmed publisher
    ..In conclusion, this report reinforces the observation that the CDKL5 phenotype overlaps with RTT and that CDKL5 analysis is recommended in patients with a seizure disorder commencing during the first months of life. ..
  52. Lonetti G, Angelucci A, Morando L, Boggio E, Giustetto M, Pizzorusso T. Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice. Biol Psychiatry. 2010;67:657-65 pubmed publisher
    ..Thus, environmental factors should be taken into account when analyzing phenotypes of MeCP2 knockout mice, an accepted model of RTT. Early EE might be beneficial in RTT patients. ..
  53. O Connor R, Zayzafoon M, Farach Carson M, Schanen N. Mecp2 deficiency decreases bone formation and reduces bone volume in a rodent model of Rett syndrome. Bone. 2009;45:346-56 pubmed publisher
    ..Our work with a Mecp2 null mouse model suggests epigenetic regulation of bone in the Mecp2 (-/yBIRD) mice which is associated with decreased osteoblast activity rather than increased osteoclastic bone loss. ..