Elongation Inhibition by DRB Sensitivity-Inducing Factor Is Regulated by the A20 Promoter via a Novel Negative Element and NF-κB

Abstract

A20 is an immediate-early NF-κB target gene. Prior to NF-κB stimulation, the A20 promoter is bound by the polymerase II machinery to allow rapid transcription activation. Here we show that the basal A20 transcription is repressed at the level of elongation in a promoter-specific fashion. Immunodepletion in vitro and RNA interference in cultured cells suggest that the basal elongation inhibition is conferred by DRB sensitivity-inducing factor (DSIF). We have identified a negative upstream promoter element called ELIE that controls DSIF activity. Remarkably, following NF-κB stimulation, inhibition of the A20 promoter by DSIF persists, but it is now regulated by NF-κB rather than ELIE. Similar regulation by DSIF is shown for another NF-κB-responsive gene, the IκBα gene. These findings reveal an intimate and dynamic relationship between DSIF inhibition of elongation and promoter-bound transcription factors. The potential significance of the differential regulation of DSIF activity by cis-acting elements is discussed.

We thank Sandra Moshonov and Merav Revach for critical reading of the manuscript.

This work was supported by research grants from the Minerva Foundation, Germany; the Israel Science Foundation; and the Crown Endowment Fund for Immunological Research. Rivka Dikstein is an incumbent of the Martha S. Sagon Career Development Chair.