DNA methylation and transcription onset in the brain

The goal of this study was to test the state of methylation of transcription start positions in DNA that are actively involved in transcription. Materials & methods: We used sequential ChIP-bisulfite-sequencing with an antibody to RNpolII-PS5 to map the state of methylation of actively transcribing transcription start sites (TSS). Results: TSS that RNApolII-PS5 physically bind to, are ubiquitously unmethylated. TSS that appear to be both heavily methylated and transcriptionally active are truly a mixture of unmethylated TSS with bound RNApolII-PS5 in some nuclei and unbound methylated TSS in other nuclei. Conclusion: TSS DNA methylation is universally inconsistent with transcription onset and could therefore serve as a digital count of the fraction of nuclei with methylation-silenced TSS.