We established a single-molecule system for mapping combinatorial chromatin modifications. We apply this powerful method to address basic questions in epigenetic regulation during early development and in cancer models which carry mutations in chromatin regulators
Genes are often regulated by several transcription factors, which bind to regulatory DNA elements with a unique chromatin structure. We explore the patterns of TFs binding to regulatory DNA at the single-molecule level, the interplay with chromatin state, and the combinatorial interactions (cooperative or inhibitory) with other TFs in the network.
The cell-free DNA (cfDNA) that circulates in the plasma and serum of humans mostly originates from apoptosis of normal hematopoietic cells. In some physiological conditions or diseases, cfDNA may originate from a different distribution of tissues, a phenomenon that is being exploited for clinical applications. We establish methodologies to identify the tissue contribution of plasma circulating nucleosomes under different physiological conditions, that leverage the unique properties of the single-molecule chromatin profiling technology.