TY - JOUR
T1 - TFII-I down-regulates a subset of estrogen-responsive genes through its interaction with an initiator element and estrogen receptor α
AU - Ogura, Yuji
AU - Azuma, Motoki
AU - Tsuboi, Yasunori
AU - Kabe, Yasuaki
AU - Yamaguchi, Yuki
AU - Wada, Tadashi
AU - Watanabe, Hajime
AU - Handa, Hiroshi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/4
Y1 - 2006/4
N2 - 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) α 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.
AB - 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) α 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.
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U2 - 10.1111/j.1365-2443.2006.00952.x
DO - 10.1111/j.1365-2443.2006.00952.x
M3 - Article
C2 - 16611241
AN - SCOPUS:33645133717
VL - 11
SP - 373
EP - 381
JO - Genes to Cells
JF - Genes to Cells
SN - 1356-9597
IS - 4
ER -