TFII-I down-regulates a subset of estrogen-responsive genes through its interaction with an initiator element and estrogen receptor alpha.
TFII-I was initially identified as the general transcription factor that binds to initiator (Inr) elements in vitro. Subsequent studies have shown that TFII-I activates transcription of various genes either through Inr elements or through other upstream elements in vivo. Since, however, most studies so far on TFII-I have been limited to over-expression and reporter gene assays, we reevaluated the role of TFII-I in vivo by using stable knockdown with siRNA and by examining the expression of endogenous genes. Contrary to the widely accepted view, here we show that TFII-I is not important for cell viability in general but rather inhibits the growth of MCF-7 human breast cancer cells. MCF-7 cells are known to proliferate in an estrogen-dependent manner. Through analysis of TFII-I's cell-type specific growth inhibitory effect, we show evidence that TFII-I down-regulates a subset of estrogen-responsive genes, only those containing Inr elements, by recruiting estrogen receptor (ER) alpha and corepressors to these promoters. Thus, this study has revealed an unexpected new role of TFII-I as a negative regulator of transcription and cell proliferation.
Ogura
Yuji
Y
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
Azuma
Motoki
M
Tsuboi
Yasunori
Y
Kabe
Yasuaki
Y
Yamaguchi
Yuki
Y
Wada
Tadashi
T
Watanabe
Hajime
H
Handa
Hiroshi
H
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology*; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D053766:Presenilin-2; D012319:RNA Polymerase II / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020218:Response Elements / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D019473:Transcription Factors, TFII / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D047628:Estrogen Receptor alpha; D004967:Estrogens; C104259:GTF2I protein, human; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D034741:RNA, Small Interfering; D019473:Transcription Factors, TFII; D012319:RNA Polymerase II