Abstract
The transcription process is regulated by temporal interactions of transcription factors with DNA. In the last decade, computational and experimental studies revealed the residence times of transcription factors on DNA correlate with transcriptional output. Biochemical studies suggest that transcription factors exhibit bi-exponential dynamics, attributed to the binary affinity model composed of nonspecific and specific protein-DNA bindings. Recently, transcription factor residence times were shown to display a power-law pattern implicating proteinDNA affinity levels are rather continuous. Elucidating the underlying mechanisms of transcription factor residence distributions, beyond protein-DNA interaction strength, is crucial to construct a more complete understanding of transcriptional regulation. Here, by using molecular dynamics simulations of DNA and dimeric proteins, we demonstrate residence time behaviors of generic homodimeric transcription factors follow a multi-exponential pattern even with single and binary affinity levels between DNA and proteins, indicating the existence of emergent behavior. Our simulations reveal that DNA-protein clusters of various sizes contribute to this multi-exponential behavior. These findings add another layer to transcriptional regulation and, consequently, to gene expression by connecting protein concentration, DNA-protein clusters, and DNA residence times of transcription factors.
Publisher
Cold Spring Harbor Laboratory