Elongation inhibition by DRB sensitivity-inducing factor is regulated by the A20 promoter via a novel negative element and NF-kappaB.
A20 is an immediate-early NF-kappaB target gene. Prior to NF-kappaB 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-kappaB stimulation, inhibition of the A20 promoter by DSIF persists, but it is now regulated by NF-kappaB rather than ELIE. Similar regulation by DSIF is shown for another NF-kappaB-responsive gene, the IkappaBalpha 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.
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Elena
E
Ainbinder
Liat
L
Amir-Zilberstein
Yuki
Y
Yamaguchi
Hiroshi
H
Handa
Rivka
R
Dikstein
D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008954:Models, Biological; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D034622:RNA Interference; D012097:Repressor Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D035602:Transcriptional Elongation Factors; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; C481011:SUPT4H1 protein, human; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3