Identification of methylation-sensitive human transcription factors using meSMiLE-seq.

Methylation-sensitive SMiLE-seq reveals 11 human transcription factors that prefer methylated DNA and 13 that avoid it, expanding understanding of DNA modification effects.

• Why it matters: Understanding how DNA methylation influences transcription factor binding is crucial for decoding gene regulation and epigenetic mechanisms, yet many TFs' methylation sensitivities remain unknown.
• What they did: Researchers developed meSMiLE-seq, a microfluidic assay that tests 114 human TFs for binding to methylated versus unmethylated DNA, identifying binding models for 48 TFs, including known and novel methylation sensitivities.
• The result: The study uncovers specific methylation preferences among TFs, such as PRDM13 and USF3, and identifies ZHX2 as a potential Z-DNA binder, providing a versatile platform for studying DNA modifications' impact on TF binding.