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Unmethylated Promoter-Proximal Region Required for Transcription
By Trevor | February 16, 2007
A new paper published this week in PLoS Genetics provides evidence that an unmethylated region extending several hundred base pairs from the promoter of a gene is required for activation of transcription.
Genes, the functional units of heredity, are made up of DNA, which is packaged inside the nuclei of eukaryotic cells in association with a number of proteins in a structure called chromatin. In order for transcription, the process of transferring genetic information from DNA to RNA, to take place, chromatin must be decondensed to allow the transcription machinery to bind the genes that are to be transcribed. In mammals, promoters, the starting position of genes, are frequently embedded in “CpG islands,” regions with a relatively high density of the CpG dinucleotide. Paradoxically, while cytosines in the context of the CpG dinucleotide are generally methylated, CpGs flanking the start sites of genes typically remain methylation-free. As CpG methylation is associated with condensed chromatin, it is generally believed that promoter regions must remain free of methylation to allow for binding of the transcription machinery. Here, using a novel method for introducing methylated DNA into a defined genomic site, we demonstrate that DNA methylation in the promoter-proximal region of a gene is sufficient to block transcription via the generation of a chromatin structure that inhibits binding of the transcription machinery. Thus, methylation may inhibit transcription even when present outside the promoter region.
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Topics: methylation, research articles |
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