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Study Tracks Cytosine Methylation Effects on Transcription, Regulatory Features in Cells

For a paper appearing in Genome Biology, investigators at the University of Western Australia and other international centers characterize the transcriptional consequences of promoter cytosine methylation marks, which tend to prompt silencing effects. With the help of a zinc finger-DNMT3A catalytic domain fusion protein construct, RNA sequencing, chromatin immunoprecipitation sequencing, bisulfite sequencing, ATAC-seq, and other approaches, the team assessed methylation at thousands of promoters in parallel, tracking the transcription, chromatin accessibility, and histone modification effects of these methylation changes, along with the return to methylation-free promoters after the fusion protein was removed. The analyses pointed to sequence context-specific transcriptional effects, for example, while flagging promoters that resisted repression and unearthing other regulatory clues. "These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated," they write.