Sunney Xie: Genome-wide single-cell and single-molecule foot printing of transcription factors with deaminase

Decades of research have established that mammalian transcription factors (TFs) bind to each gene’s regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. We have developed a technique to measure TFs’ binding sites on the human genome with a near single- base resolution by foot printing with deaminase (FOODIE) on a single-molecule and single-cell basis.

Single-molecule sequencing reads after enzymatic deamination allow detection of the TF binding fraction on a particular footprint and the binding cooperativity of any two adjacent TFs, which can be either positive or negative. Single-cell FOODIE enables the detection of cell-type-specific TF footprints in a pure cell population in a heterogeneous tissue, such as the brain. We found that genes carrying out a certain biological function together in a housing-keeping correlated gene module (CGM) or a tissue-specific CGM are coordinated by shared TFs in the gene’s promoters and enhancers, respectively. Scalable and cost-effective, FOODIE offers exciting possibilities in biology and medicine.

Prof. Xiaoliang Sunney Xie is a world renown biophysical chemist. He received his BSc in chemistry from Peking University in 1984, and his PhD in physical chemistry in 1990 from UC San Diego. After a career at Pacific Northwest National Laboratory, he became the first tenured professor at Harvard University among Chinese Scholars who came to the USA since the Reform in China. As a pioneer of single molecule biophysical chemistry, coherent Raman scattering microscopy, and single cell genomics, he made major contributions to the emergence of these fields.

Furthermore, Xie has made significant advances on medical applications of label-free optical imaging and single cell genomics. In particular, his inventions have been used in in vitro fertilization and have benefited thousands of couples in China in avoiding the transmission of their monogenic diseases to their newborns. In addition, Prof. Xie has trained more than 100 graduate students and postdocs, many of whom have become professors at more than 40 major universities around the world. Since 2010, he has been the Director of Biodynamics Optical Imaging Center (BIOPIC) at Peking University, and in 2016 he became the Director of Beijing Advanced Innovation Center for Genomics (ICG).

Prof. Xie is a member of the US National Academy of Sciences and the US National Academy of Medicine. Among his numerous honors are the Albany Medical Center Prize in Medicine and Biomedical Research, the American Chemical Society's Peter Debye Award and the Biophysical Society Founders' Award. As of April 2024, Prof. Xie has published over 230 papers, and H-Index is 127. Prof. Xie's current research interests include scientific research, technological research, and medical research.

Read more about his research here.

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