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The impact of MECP2 mutations in the expression patterns of Rett syndrome patients

, : The impact of MECP2 mutations in the expression patterns of Rett syndrome patients. Human Genetics 116(1-2): 91-104

Rett syndrome (RTT), the second most common cause of mental retardation in females, has been associated with mutations in MeCP2, the archetypical member of the methyl-CpG binding domain (MBD) family of proteins. MeCP2 additionally possesses a transcriptional repression domain (TRD). We have compared the gene expression profiles of RTT- and normal female-derived lymphoblastoid cells by using cDNA microarrays. Clustering analysis allowed the classification of RTT patients according to the localization of the MeCP2 mutation (MBD or TRD) and those with clinically diagnosed RTT but without detectable MeCP2 mutations. Numerous genes were observed to be overexpressed in RTT patients compared with control samples, including excellent candidate genes for neurodevelopmental disease. Chromatin immunoprecipitation analysis confirmed that binding of MeCP2 to corresponding promoter CpG islands was lost in RTT-derived cells harboring a mutation in the region of the MECP2 gene encoding the MBD. Bisulfite genomic sequencing demonstrated that the majority of MeCP2 binding occurred in DNA sequences with methylation-associated silencing. Most importantly, the finding that these genes are also methylated and bound by MeCP2 in neuron-related cells suggests a role in this neurodevelopmental disease. Our results provide new data of the underlying mechanisms of RTT and unveil novel targets of MeCP2-mediated gene repression.


PMID: 15549394

DOI: 10.1007/s00439-004-1200-0

Other references

Benzing, G.; DeForest, D.; Kaplan, S., 1966: Multiple-line single-reservoir automatic cardiotomy blood return system. Journal of Thoracic and Cardiovascular Surgery 51(2): 238-243

Davidson R.J.; Schwartz G.E., 1977: Patterns of occipital and sensori motor electro encephalogram during self generated visual and kinesthetic imagery. Psychophysiology 14(1): 85

Lelimousin, Mël.; Noirclerc-Savoye, M.; Lazareno-Saez, C.; Paetzold, B.; L.V.t, S.; Chazal, R.; Macheboeuf, P.; Field, M.J.; Bourgeois, D.; Royant, A., 2009: Intrinsic dynamics in ECFP and Cerulean control fluorescence quantum yield. Enhanced cyan fluorescent protein (ECFP) and its variant Cerulean are genetically encoded fluorophores widely used as donors in FRET-based cell imaging experiments. First, we have confirmed through denaturation experiments that the double-peak spe...

Freihofer, H.P., 1987: Sagittal sliding osteotomy of the alveolar process of the mandible. A modification of Hofer's osteotomy. A modification of Hofer's (1942) osteotomy of the alveolar process of the lower jaw is described. Under certain circumstances it is possible to cut the alveolar process sagittally. Thereby a gap in the alveolar process is avoided and there is...

Friman, P.C.; Larzelere, R.; Finney, J.W., 1994: Exploring the relationship between thumb-sucking and psychopathology. Studied the relationship between chronic thumb-sucking and behavior problems reflective of psychopathology. Compared scores on the Child Behavior Checklist (CBCL) and Eyberg Child Behavior Inventory (ECBI) for matched samples of thumb-sucking, ref...

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