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TFII‐I down‐regulates a subset of estrogen‐responsive genes through its interaction with an initiator element and estrogen receptor α
Author(s) -
Ogura Yuji,
Azuma Motoki,
Tsuboi Yasunori,
Kabe Yasuaki,
Yamaguchi Yuki,
Wada Tadashi,
Watanabe Hajime,
Handa Hiroshi
Publication year - 2006
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2006.00952.x
Subject(s) - biology , gene knockdown , estrogen receptor , transcription factor , nuclear receptor , hormone response element , reporter gene , microbiology and biotechnology , estrogen , promoter , regulator , transcription (linguistics) , pelp 1 , cancer research , gene , gene expression , endocrinology , genetics , cancer , breast cancer , linguistics , philosophy
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