DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation.
Transcription elongation factor DSIF/Spt4-Spt5 is capable of promoting and inhibiting RNA polymerase II elongation and is involved in the expression of various genes. While it has been known for many years that DSIF inhibits elongation in collaboration with the negative elongation factor NELF, how DSIF promotes elongation is largely unknown. Here, an activity-based biochemical approach was taken to understand the mechanism of elongation activation by DSIF. We show that the Paf1 complex (Paf1C) and Tat-SF1, two factors implicated previously in elongation control, collaborate with DSIF to facilitate efficient elongation. In human cells, these factors are recruited to the FOS gene in a temporally coordinated manner and contribute to its high-level expression. We also show that elongation activation by these factors depends on P-TEFb-mediated phosphorylation of the Spt5 C-terminal region. A clear conclusion emerging from this study is that a set of elongation factors plays nonredundant, cooperative roles in elongation. This study also shows unambiguously that Paf1C, which is generally thought to have chromatin-related functions, is involve directlyd in elongation control.
Chen
Yexi
Y
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Yamaguchi
Yuki
Y
Tsugeno
Yuta
Y
Yamamoto
Junichi
J
Yamada
Tomoko
T
Nakamura
Mitsuhiro
M
Hisatake
Koji
K
Handa
Hiroshi
H
D015971:Gene Expression Regulation, Enzymologic; D016762:Genes, fos / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D035602:Transcriptional Elongation Factors
D009687:Nuclear Proteins; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II