Differential regulation of NF-kappaB by elongation factors is determined by core promoter type.
NF-kappaB transcription factors activate genes important for immune response, inflammation, and cell survival. P-TEFb and DSIF, which are positive and negative transcription elongation factors, respectively, both regulate NF-kappaB-induced transcription, but the mechanism underlying their recruitment to NF-kappaB target genes is unknown. We show here that upon induction of NF-kappaB, a subset of target genes is regulated differentially by either P-TEFb or DSIF. The regulation of these genes and their occupancy by these elongation factors are dependent on the NF-kappaB enhancer and the core promoter type. Converting a TATA-less promoter to a TATA promoter switches the regulation of NF-kappaB from DSIF to P-TEFb. Accumulation or displacement of DSIF and P-TEFb is dictated by the formation of distinct initiation complexes (TFIID dependent or independent) on the two types of core promoter. The underlying mechanism for the dissociation of DSIF from TATA promoters upon NF-kappaB activation involves the phosphorylation of RNA polymerase II by P-TEFb. The results highlight a regulatory link between the initiation and the elongation phases of the transcription reaction and broaden our comprehension of the NF-kappaB pathway.
Amir-Zilberstein
Liat
L
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Ainbinder
Elena
E
Toube
Leanne
L
Yamaguchi
Yuki
Y
Handa
Hiroshi
H
Dikstein
Rivka
R
D000818:Animals; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010768:Phosphoserine / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012319:RNA Polymerase II / Q000378:metabolism; D016385:TATA Box / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors
D016328:NF-kappa B; D009687:Nuclear Proteins; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D010768:Phosphoserine; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II