Upstream Stimulatory Factor (USF) Is Recruited into a Steroid Hormone-triggered Regulatory Circuit by the Estrogen-inducible Transcription Factor δEF1
In the past decade, investigation into steroid hormone signaling has focused on the mechanisms of steroid hormone receptors as they act as signaling molecules and transcription factors in cells. However, the majority of hormone-responsive genes are not directly regulated by hormone receptors. These...
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Published in | The Journal of biological chemistry Vol. 277; no. 37; p. 33890 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
13.09.2002
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Online Access | Get full text |
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Summary: | In the past decade, investigation into steroid hormone signaling has focused on the mechanisms of steroid hormone receptors
as they act as signaling molecules and transcription factors in cells. However, the majority of hormone-responsive genes are
not directly regulated by hormone receptors. These genes are termed secondary response genes. To explore the molecular mechanisms
by which the steroid hormone estrogen regulates secondary response genes, the ovalbumin ( Ov ) gene was analyzed. Three protein-protein complexes (Chirp-I, -II, -III), which do not contain the estrogen receptor, are
induced by estrogen to bind to the 5â²-flanking region of the Ov gene. The Chirp-III DNA binding site, which is required for estrogen induction, binds a complex of proteins that contains
the estrogen-inducible transcription factor δEF1. Experiments undertaken to identify proteins complexed with δEF1 led to the
elucidation of a novel mechanism of action of upstream stimulatory factor-1 (USF-1), which involves its tethering to the Ov gene 5â²-flanking region by δEF1. Gel mobility shift assays and co-immunoprecipitation experiments identify USF-1 as a component
of Chirp-III. However, USF-1 is not able to bind to the Chirp-III site independently. In addition, USF-1 overexpression is
able to induce Ov gene promoter activity in transfection experiments. USF-1 can also potentiate the induction of the Ov gene by the transcription factor δEF1. Moreover, mutating the δEF1 binding sites in the 5â²-flanking region of the Ov gene abrogates induction of the gene by USF-1. These data begin to establish a molecular mechanism by which hormone-inducible
transcription factors and ubiquitous transcription factors cooperate to regulate estrogen-induced secondary response gene
expression. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M204399200 |