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J Biol Chem, Vol. 274, Issue 11, 7072-7081, March 12, 1999
From the Department of Cancer Biology, Lerner Research Institute,
Cleveland Clinic Foundation, Cleveland, Ohio 44195 and the
To better understand the function of nuclear
factor I (NFI) proteins in transcription, we have used transient
transfection assays to assess transcriptional modulation by NFI
proteins on the NFI-dependent mouse mammary tumor virus
(MMTV) promoter. Expression of NFI-C or NFI-X, but not NFI-A or NFI-B
proteins, represses glucocorticoid induction of the MMTV promoter in
HeLa cells. Repression is DNA binding-independent as a deletion
construct expressing the NH2-terminal 160 residues of
NFI-C represses but does not bind DNA. Repression by NFI-C is cell
type-dependent and occurs in HeLa and COS-1 cells but not
293 or JEG-3 cells. NFI-C does not repress progesterone induction of
the MMTV promoter in HeLa cells, suggesting that progesterone induction
of the promoter differs mechanistically from glucocorticoid induction.
NFI-C-mediated repression is alleviated by overexpression of
glucocorticoid receptor (GR), suggesting that NFI-C represses the MMTV
promoter by preventing GR function. However, repression by NFI-C occurs
with only a subset of glucocorticoid-responsive promoters, as the
chimeric NFIGRE
Nuclear Factor I-mediated Repression of the Mouse Mammary
Tumor Virus Promoter Is Abrogated by the Coactivators p300/CBP and
SRC-1
,
Department of Biochemistry, Case Western Reserve
University, Cleveland, Ohio 44106
-gal promoter that is activated by GR is not
repressed by NFI-C. Since the coactivator proteins p300/CBP, SRC-1A,
and RAC3 had previously been shown to function at steroid
hormone-responsive promoters, we asked whether they could influence
NFI-C-mediated repression of MMTV expression. Expression of p300/CBP or
SRC-1A alleviates repression by NFI-C, whereas RAC3 has no effect. This
abrogation of NFI-C-mediated repression by p300/CBP and SRC-1A suggests
that repression by NFI-C may occur by interference with coactivator function at the MMTV promoter.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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