Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene

Roland Schüle; Kazuhiko Umesono; David J. Mangelsdorf; Jack Bolado; J. Wesley Pike; Ronald M. Evans

doi:10.1016/0092-8674(90)90531-I

Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene

Roland Schüle, Kazuhiko Umesono, David J. Mangelsdorf, Jack Bolado, J. Wesley Pike, Ronald M. Evans

Research output: Contribution to journal › Article › peer-review

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Abstract

We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D₃. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.

Original language	English (US)
Pages (from-to)	497-504
Number of pages	8
Journal	Cell
Volume	61
Issue number	3
DOIs	https://doi.org/10.1016/0092-8674(90)90531-I
State	Published - May 4 1990

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/0092-8674(90)90531-I

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title = "Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene",

abstract = "We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D3. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.",

author = "Roland Sch{\"u}le and Kazuhiko Umesono and Mangelsdorf, {David J.} and Jack Bolado and Pike, {J. Wesley} and Evans, {Ronald M.}",

note = "Funding Information: We thank Drs. William W. Lamph and lnder Verma for plasmids. Special thanks to Na Yang for advice on the bacterial expression system. We also thank Ester Banayo, Estelita Ong. Mehran Hamidi, and Kevin Murakami for expert assistance, the members of the Evans laboratory and Drs. Marc Montminy and lnder Verma for discussion and critical reading of the manuscript, and Elaine Stevens for administrative assistance and help in the preparation of the manuscript. R. S. is supported by a postdoctoral fellowship of the Deutsche Forschungs-gemeinschaft. J. W. P is an established Investigator of the American Heart Association. R. M. E. is an investigator of the Howard Hughes Medical Institute. This work was supported by tine Howard Hughes Medical Institute, the National Institutes of Health, and the Mathers Foundation.",

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AU - Schüle, Roland

AU - Umesono, Kazuhiko

AU - Mangelsdorf, David J.

AU - Bolado, Jack

AU - Pike, J. Wesley

AU - Evans, Ronald M.

N1 - Funding Information: We thank Drs. William W. Lamph and lnder Verma for plasmids. Special thanks to Na Yang for advice on the bacterial expression system. We also thank Ester Banayo, Estelita Ong. Mehran Hamidi, and Kevin Murakami for expert assistance, the members of the Evans laboratory and Drs. Marc Montminy and lnder Verma for discussion and critical reading of the manuscript, and Elaine Stevens for administrative assistance and help in the preparation of the manuscript. R. S. is supported by a postdoctoral fellowship of the Deutsche Forschungs-gemeinschaft. J. W. P is an established Investigator of the American Heart Association. R. M. E. is an investigator of the Howard Hughes Medical Institute. This work was supported by tine Howard Hughes Medical Institute, the National Institutes of Health, and the Mathers Foundation.

PY - 1990/5/4

Y1 - 1990/5/4

N2 - We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D3. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.

AB - We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D3. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.

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Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene

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