Heng Xu, Shanghai Jiao Tong University
601 Pao Yue-Kong Library
Regulated gene activity is fundamental to life, driving distinct cellular behaviors at any given moment. To date, a precise mechanistic understanding of the regulation of individual gene copies in a single cell is still missing. Specifically, it has been reported that gene activity in individual cells is highly stochastic, but how this stochastic kinetics is achieved and how it is modulated by the transcription factors that regulate gene expression remain largely unknown. We address this question using the Bicoid (Bcd) transcription factor and hunchback (hb) gene in early Drosophila embryos. We measure, simultaneously, the number of nascent hb mRNAs, nuclear Bcd concentration, and number of bound Bcd proteins, at individual gene loci. Using stochastic theoretical analysis, we find that Bcd modulates the probability of hb switching to an active transcriptional state, while not affecting the probabilities of transcription initiation or gene inactivation. Gene activation is achieved through the cooperative binding of ~6 Bcd copies, while additional Bcd binding states also exist with unknown function. In contrast to Bcd, binding of the Hunchback transcription factor represses hb transcription. Our theoretical analysis also predicts surprising discontinuities in the distribution of nascent mRNA, a feature which we verify experimentally. Our research will help understand the role of gene regulation in embryo development and will provide a general experimental and theoretical framework to decipher gene regulation in other biological systems.
Dr. Heng Xu obtained his Bachelor’s Degree in Physics from the Department for Intensive Instruction at Nanjing University in 2003. He then moved to the Department of Physics at Brown University where he obtained his Ph.D. in Physics in 2010. After graduation, he took a postdoctoral position in the Department of Biochemistry & Molecular Biology at Baylor College of Medicine, where he received a Burroughs Wellcome Fund Career Award at the Scientific Interface in 2014. In 2017, Dr. Xu was selected to the Thousand Talents Program for Young Professionals and joined the faculty of the Institute of Natural Sciences and the School of Physics and Astronomy at Shanghai Jiao Tong University.