Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.

TET enzymes' oxidation of 5-methylcytosine is influenced by sequence context, affecting 5hmC persistence and shaping DNA hydroxymethylation landscapes.

• Why it matters: Understanding how TET enzymes select and modify cytosine bases is crucial for deciphering epigenetic regulation and DNA demethylation mechanisms in mammalian genomes.
• What they did: The study used a high-throughput enzymology approach to analyze 5mC, 5hmC, and 5fC/5caC at base resolution across hundreds of sites, revealing distinct sequence-dependent effects on 5hmC generation and decay.
• The result: Findings show that flanking bases differentially impact 5hmC stability in duplex DNA and that these preferences are absent in single-stranded DNA, indicating TET-intrinsic sequence biases influence cellular 5hmC patterns.