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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/

In my lecture, I will showcase how designing new materials and exploring their fundamental properties can lead to innovative concepts and practical applications in organic chemistry. We will begin by discussing the synthesis of novel halo-organic compounds that enable the stereoselective catalytic synthesis of biologically relevant chiral organofluorides.     The talk will primarily focus on the versatile chemistry of N-Heterocyclic Nitrenium ions (NHNs) – the nitrogen-based analogs of ubiquitous N-Heterocyclic Carbenes. We will demonstrate their unique coordination abilities, analyze their properties, and highlight their role in stabilizing elusive species.1,2 Nitrenium ions represent a novel family of nitrogen-based Lewis acids3 and serve as efficient metal-free catalysis, frustrated Lewis pairs partners4 and platform for isolating valuable radicals.5 Finally, we will demonstrate how the fundamental understanding nitrenium properties led to the development of triazenolysis reaction - an aza-version of the canonical alkene ozonolysis.6References:[1] Nat. Chem. 2011, 5, 525.[2] Chem.Sci. 2014, 5, 1305.[3] J. Am. Chem. Soc. 2017, 139, 4062.[4] Angew. Chem. Int. Ed. 2020, 59, 23476.[5] J. Am. Chem. Soc. 2022, 144, 23642; J. Am. Chem. Soc. 2024, 146, 19474.[6] Nat. Chem. 2025, 17, 101.

How do biological networks evolve and expand? We study these questions in the context of the plant collaborative-non-self recognition self-incompatibility system. Self-incompatibility evolved to avoid self-fertilization among plants. It relies on specific molecular recognition between highly diverse proteins expressed in the female and male reproductive organs, such that the combination of proteins an individual possesses determines its mating partners, defining distinct ‘mating specificities’. Although a few dozen mating specificities are known from population surveys, previous models struggled to pinpoint the evolutionary trajectories by which new specificities evolved. We construct a novel theoretical framework, synthesizing evolutionary and biophysical models, that crucially affords interaction promiscuity and multiple distinct partners per protein, as is seen in empirical findings. We demonstrate spontaneous self-organization of the population into distinct 'classes' with full between-class compatibility and a dynamic long-term balance between class emergence and decay.Our work highlights the importance of molecular recognition promiscuity to network evolvability. Promiscuity was found in additional systems suggesting that our framework could be more broadly applicable. FOR THE LATEST UPDATES AND CONTENT ON SOFT MATTER AND BIOLOGICAL PHYSICS AT THE WEIZMANN, VISIT OUR WEBSITE: https://www.biosoftweizmann.com/