Cooperative action in eukaryotic gene regulation: physical properties of a viral example

TL;DR

This paper models the physical properties of the Epstein-Barr virus's gene regulation switch, revealing how multiple binding sites and competition between factors create a sharp transition between latency states.

Contribution

It introduces a physico-chemical model explaining the sharpness of the EBV latency switch through cooperative and competitive binding mechanisms.

Findings

Large number of binding sites enhances switch sharpness.

Cooperative binding increases Hill coefficient.

Competition between viral and host factors influences gene regulation.

Abstract

The Epstein-Barr virus (EBV) infects more than 90% of the human population, and is the cause of several both serious and mild diseases. It is a tumorivirus, and has been widely studied as a model system for gene (de)regulation in human. A central feature of the EBV life cycle is its ability to persist in human B cells in states denoted latency I, II and III. In latency III the host cell is driven to cell proliferation and hence expansion of the viral population, but does not enter the lytic pathway, and no new virions are produced, while the latency I state is almost completely dormant. In this paper we study a physico-chemical model of the switch between latency I and latency III in EBV. We show that the unusually large number of binding sites of two competing transcription factors, one viral and one from the host, serves to make the switch sharper (higher Hill coefficient), either by cooperative binding between molecules of the same species when they bind, or by competition between the two species if there is sufficient steric hindrance.