Sunney Xie - The Central Dogma Choreography: Regulation of Gene Modules via Transcription Factor

Professor Xie shared his group’s insights on using single-molecule microscopy to study the central dogma of molecular biology, in particular gene regulation by transcription factors in human cells. In prokaryotic cells, one transcription factor controls the expression of several genes carrying out a particular biological function together. However, in human cells, each gene encodes for one protein, and is controlled by a combination of transcription factors. Several or tens of proteins within a correlated gene module interact with each other to carry out a particular biological function. Using Tn5 transposase, Professor Xie's group determined the three-dimensional structure of a single human cell for the first time in 2018. They recently found that expressed genes in a correlated gene module are not clustered together in the euchromatin space in a nucleus, but rather regulated and synchronized by shared transcription factors. They recently discovered a double-stranded DNA deaminase, which can convert cytosine to uracil, followed by conversion from uracil to thymine after PCR amplification. As such, they were able to map the genome-wide binding motifs of transcription factors on DNA via FOOt-printing by DeamInasE (FOODIE). This method can measure not only transcription factors’ binding fractions but also their cooperativity in open chromatin regions, and will advance our understanding of eukaryotic gene regulation.