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[Lecture] Deciphering Transcriptional Regulation via Single-Molecule Quantification of Transcription Factor Binding in situ
Nov. 27, 2023
Speaker: Dr. Heng XU, Associate Professor, Institute of Natural Sciences and the School of Physics and Astronomy at Shanghai Jiao Tong University

Time: 13:00-14:00 p.m., November 27, 2023, GMT+8

Venue: B101, Lui Che-woo Building, PKU


Gene transcription is controlled by the binding of transcription factors (TFs) to specific DNA regulatory sequences. However, the kinetic mechanism underlying this process remains elusive due to the challenge of detecting TF binding signals of individual gene loci in a single cell. Here, we develop a single-molecule fluorescent imaging method to quantify the absolute molecule number of bound TFs, epigenetically modified histones, and nascent mRNAs at individual hunchback (hb) gene loci in early Drosophila embryos. We find that key TFs involved in hb regulation create a broad distribution of binding states through nonequilibrium cooperative binding, which is associated with the deprivation of specific histone modifications. Using theoretical analysis, we decipher how different TF binding states modulate the stochastic kinetics of hb transcription. These results provide a general framework for uncovering the mechanisms of complex gene regulation at the single-cell and single-molecule level.

Source: School of Life Sciences, PKU