FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH.
We report that the chromatin-specific transcription elongation factor FACT functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and NELF (negative elongation factor). We find that the kinase activity of TFIIH is dispensable for this activity, demonstrating that TFIIH-mediated CTD phosphorylation is not involved in the regulation of FACT and DSIF/NELF activities. Thus, we propose a novel transcriptional regulatory network in which DSIF/NELF inhibition of transcription is prevented by P-TEFb in cooperation with FACT. This study uncovers a novel role for FACT in the regulation of transcription on naked DNA that is independent of its activities on chromatin templates. In addition, this study reveals functional differences between P-TEFb and TFIIH in the regulation of transcription.
Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
T
T
Wada
G
G
Orphanides
J
J
Hasegawa
D K
DK
Kim
D
D
Shima
Y
Y
Yamaguchi
A
A
Fukuda
K
K
Hisatake
S
S
Oh
D
D
Reinberg
H
H
Handa
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors
D004268:DNA-Binding Proteins; C492141:DSIF protein, Drosophila; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C489543:SSRP protein, Drosophila; C073537:SSRP1 protein, human; C481011:SUPT4H1 protein, human; C112224:SUPT5H protein, human; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D035602:Transcriptional Elongation Factors; C118437:negative elongation factor; D051758:Transcription Factor TFIIH; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II