TAILIEUCHUNG - Báo cáo khoa học: SYMPOSIUM 1: FUNCTIONAL GENOMICS, PROTEOMICS AND BIOINFORMATICS

The DNA of every cell in the body carries a pattern of chemical modifications due to the methylation of cytosine in the dinucleo-tide sequence 5¢CG. It is thought that these chemical marks help to define the pattern of gene expression that is appropriate for each cell type. | Symposium Abstracts SYMPOSIUM 1 FUNCTIONAL GENOMICS PROTEOMICS AND BIOINFORMATICS . Epigenetics DNA Methylation and Far Beyond IL The role of MeCP2 in the brain A. Bird P. Skene R. Illingworth and J. Guy Wellcome Trust Centre for Cell Biology University of Edinburgh Edinburgh UK The DNA of every cell in the body carries a pattern of chemical modifications due to the methylation of cytosine in the dinucleotide sequence 5 CG. It is thought that these chemical marks help to define the pattern of gene expression that is appropriate for each cell type. The nuclear protein MeCP2 was originally discovered because of its ability to specifically bind to methylated CG sites but not to CGs lacking the methyl moiety. Because of its DNA binding preference it was hypothesised that MeCP2 interprets the DNA methylation signal. A considerable body of evidence indicates that DNA methylation causes gene silencing and in line with this view early evidence established that MeCP2 can attract molecular machinery that contains enzymes capable of altering chromatin structure for example by removing acetyl groups from histone tails. A plausible hypothesis is therefore that MeCP2 binds to methylated DNA and recruits deacetylase activity so that the chromatin environment becomes incompatible with efficient transcription. This scenario predicts that the absence of MeCP2 as in neurons of patients with the autism spectrum disorder Rett Syndrome will cause inappropriate gene expression due to relaxed repression. Decisive evidence supporting this prediction has proven elusive so far and other potential functions for MeCP2 have been proposed - for example that it is an activator of transcription or a regulator of messenger RNA splicing. The functional significance of MeCP2 will be assessed in the light of studies of the structure and dynamics of the interaction between MeCP2 and methylated DNA at the molecular level. At the level of brain physiology the unexpected reversibility of Rett .

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