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Memory effects of transcription regulator−DNA interactions in bacteria
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-10-03 , DOI: 10.1073/pnas.2407647121
Won Jung, Tai-Yen Chen, Ace George Santiago, Peng Chen

Memory effect refers to the phenomenon where past events influence a system’s current and future states or behaviors. In biology, memory effects often arise from intra- or intermolecular interactions, leading to temporally correlated behaviors. Single-molecule studies have shown that enzymes and DNA-binding proteins can exhibit time-correlated behaviors of their activity. While memory effects are well documented and studied in vitro, no such examples exist in cells to our knowledge. Combining single-molecule tracking (SMT) and single-cell protein quantitation, we find in living Escherichia coli cells distinct temporal correlations in the binding/unbinding events on DNA by MerR- and Fur-family metalloregulators, manifesting as memory effects with timescales of ~1 s. These memory effects persist irrespective of the type of the metalloregulators or their metallation states. Moreover, these temporal correlations of metalloregulator–DNA interactions are associated with spatial confinements of the metalloregulators near their DNA binding sites, suggesting microdomains of ~100 nm in size that possibly result from the spatial organizations of the bacterial chromosome without the involvement of membranes. These microdomains likely facilitate repeated binding events, enhancing regulator−DNA contact frequency and potentially gene regulation efficiency. These findings provide unique insights into the spatiotemporal dynamics of protein–DNA interactions in bacterial cells, introducing the concept of microdomains as a crucial player in memory effect–driven gene regulation.
更新日期:2024-10-03
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