GSE134078
Tissue-specific 5-hydroxymethylcytosine landscape of the human genome
5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions. Overall design: We used CATCH-Seq which is a bisulfite-free, base-resolution method for the genome-wide detection of 5hmC, to detect human tissues 5hmC pattern. Our method is based on: (1) selective oxidation of 5hmC to 5fC ; (2) subsequent labeling of the newly generated 5fC; and (3) 5fC labeling adduct caused C-to-T transition during DNA amplification.We then applied CATCH-seq to genomic DNA isolated from human tissues respectively.