Kavli Affiliate: Ariel Amir
| First 5 Authors: Wencheng Ji, Ori Hachmo, Naama Barkai, Ariel Amir,
| Summary:
Transcription Factors (TFs) are proteins crucial for regulating gene
expression. Effective regulation requires the TFs to rapidly bind to the
correct target, enabling the cell to respond timely to various stimuli such as
nutrient availability or toxin presence. At the same time, the search process
is limited by slow diffusive movement and ‘false’ targets in DNA – segments of
DNA sequences that are similar to the true target. In eukaryotic cells most TFs
have an Intrinsically Disordered Region (IDR), which is a long, flexible
polymeric tail comprised of hundreds of amino acids. Recent experimental
findings indicate that the IDR of certain TFs plays a crucial role in the
search process. However, the principles underlying the IDR’s role remain
unclear. Here, we reveal key design principles of the IDR related to TF binding
affinity and search time. Our results indicate a significant enhancement in
both of these aspects attributed to the presence of the IDR. Additionally, we
propose experiments to verify these theoretical predictions.
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