[Methylation and expression of the FMR1 gene]

In this paper we present a brief review on DNA methylation, the enzymes and proteins involved in the repression complex and the importance of methylation of FMR1 gene in fragile X syndrome.

Methylation status of control region in the genome plays a critical role in the regulation of gene expression. In susceptible genes containing CpG island in the promoter, cytosine methylation favors a repressive chromatin structure that prevents the binding of transcriptional activators to the promoter. The enzyme DNA methyltransferase transfers a methyl group from the S-adenosylmethionine to the 5 carbon of cytosine in the CG sequences. Several proteins have been described that recognize the methyl cytosine and recruit the co-repressor and the histones deacetylases. The lost of the acetyl groups produces the compacting of the chromatin. Fragile X syndrome is due, in the majority of the cases, to the expansion above a threshold of the CGG repeats in the first exon of FMR1 gene. These expansions are concomitant with the methylation of the promoter and the silencing of FMR1.

DNA methylation is a tag that enables different phenotypic expression from an identical nucleotide sequence. Aberrant methylation is the cause of different pathologies including fragile X syndrome. The comprehension of the mechanisms by which methylation induces the silencing of the genes and the study of agents that could revert this process are important for the treatment of these diseases.