CpG islands are topological sinks for transcription-induced DNA supercoiling

Highly transcribed CpG island (CGI) promoters accumulate elevated negative DNA supercoiling compared with highly transcribed non-CGI promoters, as measured genome-wide by Twist-seq.

• Why it matters: Promoter torsional stress from transcription is known to be handled by topoisomerases, but how promoter DNA sequence and chromatin architecture shape where negative supercoiling accumulates is unclear.
• What they did: Twist-seq quantified supercoiling across the genome, and coarse-grained molecular dynamics simulations linked CGI intrinsic DNA properties to localized melting and DNA writhe in promoter-proximal nucleosome-free regions.
• The result: CGI promoters show depletion in Top1 and increased ssDNA in vivo, and they are linked to increased somatic mutation rates at highly expressed CGI promoters, implying a buffering role with a possible genome-stability cost.

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