Interdependence between DNA methylation and transcription

Cytosine methylation, a common form of DNA modification that antagonizes transcriptional initiation, is found at transposons and repeats in vertebrates, plants, and fungi. Here we have mapped DNA methylation in the entire Arabidopsis thaliana genome at high resolution. DNA methylation covers transposons and is present within about 20% of Arabidopsis genes. Methylation within genes is conspicuously biased away from gene ends, suggesting a dependence on RNA polymerase transit. Genic methylation is strongly influenced by transcription: moderately transcribed genes are most likely to be methylated, while genes at either extreme are least likely. Small RNAs are enriched at methylated genes, which suggests that aberrant transcription triggers genic methylation. Transcription is in turn influenced by methylation: short methylated genes are poorly expressed, and loss of methylation in the body of a gene leads to enhanced transcription. Our results indicate that genic transcription and DNA methylation are closely interwoven processes. Keywords: whole genome profiling, DNA methylation, met1-6 expression All experiments were done using two channels per chip. Two microarray experiments compared immunoprecipitated, methylated DNA to control genomic DNA. A third microarray experiment used a methylation sensitive restriction enzyme (HpyCH4 IV) to determine regions of differential DNA methylation in met1-6 mutant plants. Two microarray experiments for expression analysis of met1-6 mutants were done using biological replicates. Oligo (dT) primed cDNA from mutant plants was compared to oligo (dT) primed cDNA from wild type plants.