TY - JOUR
T1 - hCTR9, a component of Paf1 complex, participates in the transcription of interleukin 6-responsive genes through regulation of STAT3-DNA interactions
AU - Youn, Min Young
AU - Yoo, Hyun Seok
AU - Kim, Min Jung
AU - Hwang, Sun Young
AU - Choi, Yongwook
AU - Desiderio, Stephen V.
AU - Yoo, Joo Yeon
PY - 2007/11/30
Y1 - 2007/11/30
N2 - PAF, which is composed of Paf1, Cdc73, Ctr9, Leo1, and Rtf1, is a novel complex with multiple functions in transcription-related activities. The PAF complex interacts with histone-modifying enzymes and RNA polymerase II to regulate transcription. With general transcription regulatory potential in yeast, Hyrax/Cdc73 has been reported to associate with β-catenin to control Wnt/Wg signal-specific transcription in Drosophila. Here, we present the first evidence of IL-6 signal-specific transcriptional regulation by SH2BP1/CTR9 in mammals. Upon LPS injection of mice, we observed transient induction of the mammalian PAF complex in the liver. Inhibition of CTR9 specifically abrogated expression of IL-6-responsive genes, but had no effect on genes constitutively expressed or induced by interferon-β, TNFα, or IL-1β. The PAF complex was found in the promoter regions of IL-6-responsive HP and FGGγ, but not in the promoter region of constitutively active GAPDH. Transcriptional activation by STAT3 was inhibited when CTR9 siRNA was introduced, whereas transcriptional activation was enhanced by mCtr9 overexpression. IL-6-activated Stat3 was found to co-localize and interact with CTR9. In CTR9-depleted cells, decreased STAT3 association with the promoter regions, as well as impaired K4-trimethylation of histone H3 in the coding regions, of target genes was observed. These data suggest that CTR9 participates in the transcription of IL-6-responsive genes through the regulation of DNA association of STAT3 and modification of histone methylation.
AB - PAF, which is composed of Paf1, Cdc73, Ctr9, Leo1, and Rtf1, is a novel complex with multiple functions in transcription-related activities. The PAF complex interacts with histone-modifying enzymes and RNA polymerase II to regulate transcription. With general transcription regulatory potential in yeast, Hyrax/Cdc73 has been reported to associate with β-catenin to control Wnt/Wg signal-specific transcription in Drosophila. Here, we present the first evidence of IL-6 signal-specific transcriptional regulation by SH2BP1/CTR9 in mammals. Upon LPS injection of mice, we observed transient induction of the mammalian PAF complex in the liver. Inhibition of CTR9 specifically abrogated expression of IL-6-responsive genes, but had no effect on genes constitutively expressed or induced by interferon-β, TNFα, or IL-1β. The PAF complex was found in the promoter regions of IL-6-responsive HP and FGGγ, but not in the promoter region of constitutively active GAPDH. Transcriptional activation by STAT3 was inhibited when CTR9 siRNA was introduced, whereas transcriptional activation was enhanced by mCtr9 overexpression. IL-6-activated Stat3 was found to co-localize and interact with CTR9. In CTR9-depleted cells, decreased STAT3 association with the promoter regions, as well as impaired K4-trimethylation of histone H3 in the coding regions, of target genes was observed. These data suggest that CTR9 participates in the transcription of IL-6-responsive genes through the regulation of DNA association of STAT3 and modification of histone methylation.
UR - http://www.scopus.com/inward/record.url?scp=36849018904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36849018904&partnerID=8YFLogxK
U2 - 10.1074/jbc.M705411200
DO - 10.1074/jbc.M705411200
M3 - Article
C2 - 17911113
AN - SCOPUS:36849018904
VL - 282
SP - 34727
EP - 34734
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 48
ER -