| Summary: | Recently, new DNA modifications have been discovered in the mammalian genome, namely 5-hydroxymethylcytosine (5hmC), 5-formylcysotine (5fC) and 5-carboxylcytosine (5caC), which have broad impact in biological functions. We have been working on developing effective sequencing technologies to reveal the functional roles of these newly discovered DNA modifications in biological samples by using selective chemical labeling and low input DNA library construction technologies. We have developed chemical assisted bisulfite sequencing (CAB-Seq) for base-resolution sequencing of 5fC and 5caC, DNA immunoprecipitation-coupled chemical-modification assisted bisulfite sequencing (DIP-CAB-Seq) for genome-wide base-resolution sequencing of 5fC and 5caC, 5hmC selective chemical labeling from low input DNA (nano- Seal) for 5hmC profiling and Tet-assisted bisulfite sequencing from low input DNA (nano-TAB-Seq) for base-resolution sequencing of 5hmC. By applying these methods, we have studied the accurate distribution of these new mammalian DNA modifications and are able to study their functions in varies biological pathways and human disease. Together our studies add to a more complete picture of the dynamic epigenetic regulatory network that plays critical roles in human development and disease.
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