| Summary: | <p>5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are fundamental and distinct DNA modifications for gene regulation. To fully understand tissue-specific epigenetic mechanisms, a comprehensive human tissue atlas of these modifications is indispensable. However, existing atlases primarily rely on methylation arrays, covering only a fraction of the genome, or bisulfite sequencing, which fails to differentiate between 5mC and 5hmC. Here, we present a novel human atlas of 5mC and 5hmC for major tissues, blood cell types, and common cancer types. Our atlas encompasses 116 samples from 13 healthy tissue types, 9 blood cell types, 10 tumour types, and 2 precancerous tissue types.</p>
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<p>To unveil tissue-specific signatures of 5mC and 5hmC, we first segment the genome into blocks of correlated modification levels for each modification. Subsequently, we identify differentially modified blocks (DMBs) for healthy tissues, blood cells, and tumours. Notably, 5mC hypo DMBs and 5hmC hyper DMBs exhibit clear tissue/blood cell/tumour type specificity and mark distinct genomic loci. They are associated with tissue/blood cell/tumour type-specific gene expression and active histone modifications. Leveraging this rich sequencing data, we demonstrate that 5hmC within gene bodies better correlates with gene expression than 5mC or 5hmC in other genomic features.</p>
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<p>Our atlas serves as a valuable resource for elucidating tissue/blood cell/tumour type-specific epigenetic regulation in various biological studies and holds promise for clinical applications, such as early cancer detection.</p>
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