HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions

Gary A. Reynolds; Sandip K. Basu; Timothy F. Osborne; Daniel J. Chin; Gregorio Gil; Michael S. Brown; Joseph L. Goldstein; Kenneth L. Luskey

doi:10.1016/0092-8674(84)90549-X

HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions

Gary A. Reynolds, Sandip K. Basu, Timothy F. Osborne, Daniel J. Chin, Gregorio Gil, Michael S. Brown, Joseph L. Goldstein, Kenneth L. Luskey

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

264 Scopus citations

Abstract

The rate-limiting enzyme of cholesterol biosynthesis, HMG CoA reductase, is controlled by negative feedback regulation of transcription. We have isolated the reductase gene from a bacteriophage λ genomic library prepared from hamster UT-1 cells. The 25 kilobase gene is split into 20 exons. The 5′ untranslated and promoter regions differ from those of previously characterized genes. The 5′ untranslated region encompasses as many as 670 nucleotides; contains up to eight AUG codons upstream of the codon used to initiate translation; and has multiple transcription initiation sites as determined by S1 nuclease mapping and primer extension analysis. The promoter region lacks a characteristic TATA box and CCAAT box; is rich in G+C residues (65%); and contains repeat sequences homologous to the 21 base pair repeats of the SV40 promoter. These unusual features may be relevant to the mechanism of expression of "housekeeping" genes, particularly those that are subject to negative feedback regulation.

Original language	English (US)
Pages (from-to)	275-285
Number of pages	11
Journal	Cell
Volume	38
Issue number	1
DOIs	https://doi.org/10.1016/0092-8674(84)90549-X
State	Published - Aug 1984
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/0092-8674(84)90549-X

Cite this

@article{b3e834fae28e491195f2e0088c88fd2d,

title = "HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions",

abstract = "The rate-limiting enzyme of cholesterol biosynthesis, HMG CoA reductase, is controlled by negative feedback regulation of transcription. We have isolated the reductase gene from a bacteriophage λ genomic library prepared from hamster UT-1 cells. The 25 kilobase gene is split into 20 exons. The 5′ untranslated and promoter regions differ from those of previously characterized genes. The 5′ untranslated region encompasses as many as 670 nucleotides; contains up to eight AUG codons upstream of the codon used to initiate translation; and has multiple transcription initiation sites as determined by S1 nuclease mapping and primer extension analysis. The promoter region lacks a characteristic TATA box and CCAAT box; is rich in G+C residues (65%); and contains repeat sequences homologous to the 21 base pair repeats of the SV40 promoter. These unusual features may be relevant to the mechanism of expression of {"}housekeeping{"} genes, particularly those that are subject to negative feedback regulation.",

author = "Reynolds, {Gary A.} and Basu, {Sandip K.} and Osborne, {Timothy F.} and Chin, {Daniel J.} and Gregorio Gil and Brown, {Michael S.} and Goldstein, {Joseph L.} and Luskey, {Kenneth L.}",

note = "Funding Information: We are grateful to David W. Russell for helpful advice and criticism and to Mark Zoller for providing us with synthetic oligonucleotides. Clarice Grimes and Edith Womack provided excellent technical assistance in growing UT-1 cells. This work was supported by a research grant from the National Institutes of Health. G. A. R. is the recipient of the Lita Anne&erg Hazen Fellowship Award. T. F. O., D. J. C., and G. G. are recipients of fellowships from the Damon Runyon-Wafter Winchefl Cancer Fund, the Helen Hay Whitney Foundation, and the Juan March Foundation, respectively. K. L. L. is an Established Investigator of the American Heart Association, The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “achtisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.",

year = "1984",

month = aug,

doi = "10.1016/0092-8674(84)90549-X",

language = "English (US)",

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T2 - A negatively regulated gene with unusual promoter and 5′ untranslated regions

AU - Reynolds, Gary A.

AU - Basu, Sandip K.

AU - Osborne, Timothy F.

AU - Chin, Daniel J.

AU - Gil, Gregorio

AU - Brown, Michael S.

AU - Goldstein, Joseph L.

AU - Luskey, Kenneth L.

N1 - Funding Information: We are grateful to David W. Russell for helpful advice and criticism and to Mark Zoller for providing us with synthetic oligonucleotides. Clarice Grimes and Edith Womack provided excellent technical assistance in growing UT-1 cells. This work was supported by a research grant from the National Institutes of Health. G. A. R. is the recipient of the Lita Anne&erg Hazen Fellowship Award. T. F. O., D. J. C., and G. G. are recipients of fellowships from the Damon Runyon-Wafter Winchefl Cancer Fund, the Helen Hay Whitney Foundation, and the Juan March Foundation, respectively. K. L. L. is an Established Investigator of the American Heart Association, The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “achtisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

PY - 1984/8

Y1 - 1984/8

N2 - The rate-limiting enzyme of cholesterol biosynthesis, HMG CoA reductase, is controlled by negative feedback regulation of transcription. We have isolated the reductase gene from a bacteriophage λ genomic library prepared from hamster UT-1 cells. The 25 kilobase gene is split into 20 exons. The 5′ untranslated and promoter regions differ from those of previously characterized genes. The 5′ untranslated region encompasses as many as 670 nucleotides; contains up to eight AUG codons upstream of the codon used to initiate translation; and has multiple transcription initiation sites as determined by S1 nuclease mapping and primer extension analysis. The promoter region lacks a characteristic TATA box and CCAAT box; is rich in G+C residues (65%); and contains repeat sequences homologous to the 21 base pair repeats of the SV40 promoter. These unusual features may be relevant to the mechanism of expression of "housekeeping" genes, particularly those that are subject to negative feedback regulation.

AB - The rate-limiting enzyme of cholesterol biosynthesis, HMG CoA reductase, is controlled by negative feedback regulation of transcription. We have isolated the reductase gene from a bacteriophage λ genomic library prepared from hamster UT-1 cells. The 25 kilobase gene is split into 20 exons. The 5′ untranslated and promoter regions differ from those of previously characterized genes. The 5′ untranslated region encompasses as many as 670 nucleotides; contains up to eight AUG codons upstream of the codon used to initiate translation; and has multiple transcription initiation sites as determined by S1 nuclease mapping and primer extension analysis. The promoter region lacks a characteristic TATA box and CCAAT box; is rich in G+C residues (65%); and contains repeat sequences homologous to the 21 base pair repeats of the SV40 promoter. These unusual features may be relevant to the mechanism of expression of "housekeeping" genes, particularly those that are subject to negative feedback regulation.

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HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions

Abstract

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