Dynamical Analysis on Gene Activity in the Presence of Repressors and an Interfering Promoter

TL;DR

This paper analyzes how gene activity is regulated by repressors and interfering promoters, revealing that interference can de-repress promoters by removing repressors, especially when open complex formation is rapid.

Contribution

It introduces a dynamical analysis of gene regulation considering time scales of transcription factors and interference effects from opposing promoters.

Findings

Repression leads to bursty transcription with long quiescent periods.

Interference from an opposing promoter can de-repress a promoter by removing repressors.

De-repression is prominent when open complex formation is fast and repressor binding is slow.

Abstract

Transcription is regulated through interplay between transcription factors, an RNA polymerase(RNAP), and a promoter. Even for a simple repressive transcription factor that disturbs promoter activity at the initial binding of RNAP, its repression level is not determined solely by the dissociation constant of transcription factor but is sensitive to the time scales of processes in RNAP. We first analyse the promoter activity under strong repression by a slow binding repressor, in which case transcriptions occur in a burst, followed by a long quiescent period while a repressor binds to the operator; the number of transcriptions, the bursting and the quiescent times are estimated by reaction rates. We then examine interference effect from an opposing promoter, using the correlation function of transcription initiations for a single promoter. The interference is shown to de-repress the promoter because RNAP's from the opposing promoter most likely encounter the repressor and remove it in case of strong repression. This de-repression mechanism should be especially prominent for the promoters that facilitate fast formation of open complex with the repressor whose binding rate is slower than about 1/sec. Finally, we discuss possibility of this mechanism for high activity of promoter PR in the hyp-mutant of lambda phage.