The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MECP2  -  methyl CpG binding protein 2

Homo sapiens

Synonyms: AUTSX3, MRX16, MRX79, MRXS13, MRXSL, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MECP2


Psychiatry related information on MECP2

  • Mutations in MECP2 are associated with Rett syndrome, an X-linked neurodevelopmental disorder [6].
  • Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males [7].
  • Mutation analysis of the coding sequence of the MECP2 gene in infantile autism [8].
  • Rett syndrome (RTT) is unique among genetic, chromosomal and other developmental disorders because of its extreme female gender bias, early normal development, and subsequent developmental regression with loss of motor and language skills [9].
  • Except for Rett syndrome--attributable in most affected individuals to mutations of the methyl-CpG-binding protein 2 (MeCP2) gene--the other PDD subtypes (autistic disorder, Asperger disorder, disintegrative disorder, and PDD Not Otherwise Specified [PDD-NOS]) are not linked to any particular genetic or nongenetic cause [10].

High impact information on MECP2


Chemical compound and disease context of MECP2


Biological context of MECP2

  • Comparison of the clinical features in these patients and in a previously reported patient enables refinement of the genotype-phenotype correlation and strongly suggests that increased dosage of MECP2 results in the MR phenotype [7].
  • However, RNA interference of endogenous MECP2 does not induce the expression of the inactive SYBL1 alleles, suggesting that its silencing activity can be replaced by the other methyl-binding proteins [20].
  • RESULTS: We identified mainly silent polymorphisms within the MECP2 gene, together with four sequence alterations of unknown significance, i.e. three missense mutations (T197M, T228S, and P376S) and one substitution at position -19 in intron 3 (378-19delT) [21].
  • CONCLUSIONS: These results confirm that MECP2 mutations in males are far more rare than initially thought and call for a careful evaluation of the pathogenicity of the MECP2 missense mutations identified in mentally retarded males before genetic counseling is proposed to the relatives [21].
  • Mutations in MECP2 appear to give a growth disadvantage to both neuronal and lymphoblast cells, often resulting in skewing of X inactivation that may contribute to the large degree of phenotypic variation [22].

Anatomical context of MECP2

  • As female somatic cells are mosaic for expression of mutant MECP2, we performed single cell cloning of T lymphocytes from four RTT patients with MECP2 mutations to isolate cells expressing mutant MECP2 [23].
  • Mutations in MECP2 are primarily de novo events in the male germ line and thus lead to an excess of affected females [24].
  • However, there was no protein expression for MBD2 and MeCP2 in cancer cell lines and cancer tissues [25].
  • In HeLa cells, quantitative chromatin immunoprecipitation assays indicated that MBD2 is associated with the methylated region, while MeCP2 and MBD1 were not detected at this locus [26].
  • However, conditional mouse mutants with selective loss of Mecp2 in the brain develop clinical manifestations similar to RTT, indicating that MECP2 is exclusively required for central nervous system function [27].

Associations of MECP2 with chemical compounds


Physical interactions of MECP2


Regulatory relationships of MECP2

  • The results of this study demonstrate that MBD2 gene is expressed in all samples and MeCP2 gene is expressed in all cancer cell lines but not in BPH-1 cell line [25].
  • MeCP2 repressed transcriptional activity of PU.1 on a reporter construct with trimerized PU.1 binding sites [36].
  • We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs [3].
  • Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation [37].
  • The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. siRNA knockdown of MeCP2 elevated IkappaBalpha promoter activity, mRNA and protein expression in myofibroblasts [38].

Other interactions of MECP2

  • Considering the similar phenotypes caused by mutations in MECP2 and CDKL5, it has been suggested that the two genes play a role in common pathogenic processes [39].
  • Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3 [2].
  • MECP2 encodes methyl-CpG-binding protein 2 that acts as a transcriptional repressor for methylated gene constructs but is surprisingly not required for maintaining imprinted gene expression [2].
  • Although these histone deacetylase genes have been considered as good candidate genes for RTT our molecular analysis of these genes did not detect any mutations [40].
  • The duplications in the four patients vary in size from 0.4 to 0.8 Mb and harbor several genes, which, for each duplication, include the MR-related L1CAM and MECP2 genes [7].

Analytical, diagnostic and therapeutic context of MECP2

  • Long distance PCR coupled with long-read direct sequencing was employed to sequence the entire MECP2 gene coding region in all cases [41].
  • Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location [41].
  • METHODS: We screened by denaturing high-pressure liquid chromatography the entire coding region and flanking intronic sequences of the MECP2 gene in a cohort of 354 mentally retarded males found negative for an expansion across the FRAXA CGG repeat and in a family in which a boy and his sister were mentally retarded [21].
  • Further evaluation of the therapeutic effects of these drugs in RTT animal models is needed before clinical trials can begin [42].
  • These findings clearly call for a careful consideration of the pathogenicity of the MECP2 mutations identified in sporadic male cases before genetic counselling or prenatal diagnosis is proposed to the corresponding families [43].


  1. MECP2 is highly mutated in X-linked mental retardation. Couvert, P., Bienvenu, T., Aquaviva, C., Poirier, K., Moraine, C., Gendrot, C., Verloes, A., Andrès, C., Le Fevre, A.C., Souville, I., Steffann, J., des Portes, V., Ropers, H.H., Yntema, H.G., Fryns, J.P., Briault, S., Chelly, J., Cherif, B. Hum. Mol. Genet. (2001) [Pubmed]
  2. Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Samaco, R.C., Hogart, A., LaSalle, J.M. Hum. Mol. Genet. (2005) [Pubmed]
  3. The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth. Bernard, D., Gil, J., Dumont, P., Rizzo, S., Monté, D., Quatannens, B., Hudson, D., Visakorpi, T., Fuks, F., de Launoit, Y. Oncogene (2006) [Pubmed]
  4. MECP2 analysis in mentally retarded patients: implications for routine DNA diagnostics. Kleefstra, T., Yntema, H.G., Nillesen, W.M., Oudakker, A.R., Mullaart, R.A., Geerdink, N., van Bokhoven, H., de Vries, B.B., Sistermans, E.A., Hamel, B.C. Eur. J. Hum. Genet. (2004) [Pubmed]
  5. A new paradigm for West syndrome based on molecular and cell biology. Kato, M. Epilepsy Res. (2006) [Pubmed]
  6. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Horike, S., Cai, S., Miyano, M., Cheng, J.F., Kohwi-Shigematsu, T. Nat. Genet. (2005) [Pubmed]
  7. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Van Esch, H., Bauters, M., Ignatius, J., Jansen, M., Raynaud, M., Hollanders, K., Lugtenberg, D., Bienvenu, T., Jensen, L.R., Gecz, J., Moraine, C., Marynen, P., Fryns, J.P., Froyen, G. Am. J. Hum. Genet. (2005) [Pubmed]
  8. Mutation analysis of the coding sequence of the MECP2 gene in infantile autism. Beyer, K.S., Blasi, F., Bacchelli, E., Klauck, S.M., Maestrini, E., Poustka, A. Hum. Genet. (2002) [Pubmed]
  9. Mechanisms of Disease: neurogenetics of MeCP2 deficiency. Francke, U. Nature clinical practice. Neurology. (2006) [Pubmed]
  10. The genetics of autism. Muhle, R., Trentacoste, S.V., Rapin, I. Pediatrics (2004) [Pubmed]
  11. Testing for association between MeCP2 and the brahma-associated SWI/SNF chromatin-remodeling complex. Hu, K., Nan, X., Bird, A., Wang, W. Nat. Genet. (2006) [Pubmed]
  12. A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Mnatzakanian, G.N., Lohi, H., Munteanu, I., Alfred, S.E., Yamada, T., MacLeod, P.J., Jones, J.R., Scherer, S.W., Schanen, N.C., Friez, M.J., Vincent, J.B., Minassian, B.A. Nat. Genet. (2004) [Pubmed]
  13. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Guy, J., Hendrich, B., Holmes, M., Martin, J.E., Bird, A. Nat. Genet. (2001) [Pubmed]
  14. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Chen, R.Z., Akbarian, S., Tudor, M., Jaenisch, R. Nat. Genet. (2001) [Pubmed]
  15. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Amir, R.E., Van den Veyver, I.B., Wan, M., Tran, C.Q., Francke, U., Zoghbi, H.Y. Nat. Genet. (1999) [Pubmed]
  16. Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein. Watson, P., Black, G., Ramsden, S., Barrow, M., Super, M., Kerr, B., Clayton-Smith, J. J. Med. Genet. (2001) [Pubmed]
  17. Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins. Tryndyak, V.P., Kovalchuk, O., Pogribny, I.P. Cancer Biol. Ther. (2006) [Pubmed]
  18. Reduced folate transport to the CNS in female Rett patients. Ramaekers, V.T., Hansen, S.I., Holm, J., Opladen, T., Senderek, J., Häusler, M., Heimann, G., Fowler, B., Maiwald, R., Blau, N. Neurology (2003) [Pubmed]
  19. Multiple modes of interaction between the methylated DNA binding protein MeCP2 and chromatin. Nikitina, T., Shi, X., Ghosh, R.P., Horowitz-Scherer, R.A., Hansen, J.C., Woodcock, C.L. Mol. Cell. Biol. (2007) [Pubmed]
  20. Multiple binding of methyl-CpG and polycomb proteins in long-term gene silencing events. Matarazzo, M.R., De Bonis, M.L., Strazzullo, M., Cerase, A., Ferraro, M., Vastarelli, P., Ballestar, E., Esteller, M., Kudo, S., D'Esposito, M. J. Cell. Physiol. (2007) [Pubmed]
  21. MECP2 mutations or polymorphisms in mentally retarded boys: diagnostic implications. Bourdon, V., Philippe, C., Martin, D., Verloès, A., Grandemenge, A., Jonveaux, P. Mol. Diagn. (2003) [Pubmed]
  22. Rett syndrome: clinical review and genetic update. Weaving, L.S., Ellaway, C.J., Gécz, J., Christodoulou, J. J. Med. Genet. (2005) [Pubmed]
  23. MECP2 mutations in Rett syndrome adversely affect lymphocyte growth, but do not affect imprinted gene expression in blood or brain. Balmer, D., Arredondo, J., Samaco, R.C., LaSalle, J.M. Hum. Genet. (2002) [Pubmed]
  24. Rett syndrome in a 47,XXX patient with a de novo MECP2 mutation. Hammer, S., Dorrani, N., Hartiala, J., Stein, S., Schanen, N.C. Am. J. Med. Genet. A (2003) [Pubmed]
  25. Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2. Patra, S.K., Patra, A., Zhao, H., Carroll, P., Dahiya, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  26. Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus. Auriol, E., Billard, L.M., Magdinier, F., Dante, R. Nucleic Acids Res. (2005) [Pubmed]
  27. Rett syndrome: the complex nature of a monogenic disease. Renieri, A., Meloni, I., Longo, I., Ariani, F., Mari, F., Pescucci, C., Cambi, F. J. Mol. Med. (2003) [Pubmed]
  28. Magnetic resonance spectroscopy and analysis of MECP2 in Rett syndrome. Khong, P.L., Lam, C.W., Ooi, C.G., Ko, C.H., Wong, V.C. Pediatric neurology. (2002) [Pubmed]
  29. The impact of MECP2 mutations in the expression patterns of Rett syndrome patients. Ballestar, E., Ropero, S., Alaminos, M., Armstrong, J., Setien, F., Agrelo, R., Fraga, M.F., Herranz, M., Avila, S., Pineda, M., Monros, E., Esteller, M. Hum. Genet. (2005) [Pubmed]
  30. Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region. Lebo, R.V., Ikuta, T., Milunsky, J.M., Milunsky, A. Clin. Genet. (2001) [Pubmed]
  31. Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human gastric cancer. Fang, J.Y., Cheng, Z.H., Chen, Y.X., Lu, R., Yang, L., Zhu, H.Y., Lu, L.G. World J. Gastroenterol. (2004) [Pubmed]
  32. Methyl-CpG binding proteins are involved in restricting differentiation plasticity in neurons. Setoguchi, H., Namihira, M., Kohyama, J., Asano, H., Sanosaka, T., Nakashima, K. J. Neurosci. Res. (2006) [Pubmed]
  33. Radiation-induced molecular changes in rat mammary tissue: Possible implications for radiation-induced carcinogenesis. Loree, J., Koturbash, I., Kutanzi, K., Baker, M., Pogribny, I., Kovalchuk, O. Int. J. Radiat. Biol. (2006) [Pubmed]
  34. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Cameron, E.E., Bachman, K.E., Myöhänen, S., Herman, J.G., Baylin, S.B. Nat. Genet. (1999) [Pubmed]
  35. T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-gamma promoter via a conserved T-box half-site. Tong, Y., Aune, T., Boothby, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  36. Direct association between PU.1 and MeCP2 that recruits mSin3A-HDAC complex for PU.1-mediated transcriptional repression. Suzuki, M., Yamada, T., Kihara-Negishi, F., Sakurai, T., Oikawa, T. Oncogene (2003) [Pubmed]
  37. Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation. Zhou, Z., Hong, E.J., Cohen, S., Zhao, W.N., Ho, H.Y., Schmidt, L., Chen, W.G., Lin, Y., Savner, E., Griffith, E.C., Hu, L., Steen, J.A., Weitz, C.J., Greenberg, M.E. Neuron (2006) [Pubmed]
  38. Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Mann, J., Oakley, F., Akiboye, F., Elsharkawy, A., Thorne, A.W., Mann, D.A. Cell Death Differ. (2007) [Pubmed]
  39. CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Mari, F., Azimonti, S., Bertani, I., Bolognese, F., Colombo, E., Caselli, R., Scala, E., Longo, I., Grosso, S., Pescucci, C., Ariani, F., Hayek, G., Balestri, P., Bergo, A., Badaracco, G., Zappella, M., Broccoli, V., Renieri, A., Kilstrup-Nielsen, C., Landsberger, N. Hum. Mol. Genet. (2005) [Pubmed]
  40. Mutation analysis of the HDAC 1, 2, 8 and CDKL5 genes in Rett syndrome patients without mutations in MECP2. Huppke, P., Ohlenbusch, A., Brendel, C., Laccone, F., Gärtner, J. Am. J. Med. Genet. A (2005) [Pubmed]
  41. Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Cheadle, J.P., Gill, H., Fleming, N., Maynard, J., Kerr, A., Leonard, H., Krawczak, M., Cooper, D.N., Lynch, S., Thomas, N., Hughes, H., Hulten, M., Ravine, D., Sampson, J.R., Clarke, A. Hum. Mol. Genet. (2000) [Pubmed]
  42. Lithium and antidepressants: potential agents for the treatment of Rett syndrome. Tsai, S.J. Med. Hypotheses (2006) [Pubmed]
  43. Polymorphisms in the C-terminal domain of MECP2 in mentally handicapped boys: implications for genetic counselling. Moncla, A., Kpebe, A., Missirian, C., Mancini, J., Villard, L. Eur. J. Hum. Genet. (2002) [Pubmed]
WikiGenes - Universities