The Clore Center for Biological Physics
Date:
Lecture / Seminar
Time: 12:45-14:30
Title: Design principles of protein-DNA Recognition Specificity in Embryonic Stem Cells
Location: Nella and Leon Benoziyo Physics Building
Lecturer: David B. Lukatsky
Organizer: Clore Center for Biological Physics
Abstract: Transcription factors (TFs) bind genomic DNA regulating gene expression and deve ... Read more Transcription factors (TFs) bind genomic DNA regulating gene expression and developmental programs in embryonic stem cells (ESCs). Even though comprehensive genome-wide molecular maps for TF-DNA binding are experimentally available for key pluripotency-associated TFs, the understanding of molecular design principles responsible for TF-DNA recognition remains incomplete. In this talk, I will show that binding preferences of key pluripotency TFs exhibit bimodality in the local GC-content distribution. Sequence-dependent binding specificity of these TFs is distributed across three major contributions. First, local GCcontent is dominant in high-GC-content regions. Second, recognition of specific k-mers is predominant in low-GC-content regions. Third, short tandem repeats (STRs) are highly predictive in both low- and high-GC-content regions. In sharp contrast, binding preferences of a key oncogenic protein, c-Myc, are exclusively dominated by local GC-content and STRs in high-GC-content genomic regions. I will propose that the transition in the TF-DNA binding landscape upon ESC differentiation is solely regulated by the concentration of c-Myc, which forms a bivalent c-Myc-Max heterotetramer upon promoter binding, competing with key pluripotency factors. Taken together, these findings point out that c-Myc may significantly affect the genome-wide TF-DNA binding landscape, chromatin structure, and enhancerpromoter interactions.FOR THE LATEST UPDATES AND CONTENT ON SOFT MATTER AND BIOLOGICAL PHYSICS AT THE WEIZMANN, VISIT OUR WEBSITE: https://www.biosoftweizmann.com/Close abstract
