Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase

G. Gil, J. R. Smith, J. L. Goldstein, Clive A. Slaughter, K. Orth, M. S. Brown, T. F. Osborn

Research output: Contribution to journalArticle

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Abstract

DNA-binding proteins of the nuclear factor 1 (NF1) family recognize sequences containing TGG. Two of these proteins, termed reductase promoter factor (RPF) proteins A and B, bind to the promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a negatively regulated enzyme in cholesterol biosynthesis. In the current study, we determined the sequences of peptides derived from hamster RPF proteins A and B and used this information to isolate a cDNA, designated pNF1/Red1, that encodes RPF protein B. The peptide sequence of RPF protein A, the other reductase-related protein, suggests that it is the hamster equivalent of NF1/L, which was previously cloned from rat liver. We also isolated a hamster cDNA for an additional member of the NF1 family, designated NF1/X. Thus, the hamster genome contains at least three genes for NF1-like proteins. It is likely to contain a fourth gene, corresponding to NF1/CTF, which was previously cloned from the human. The NH2-terminal sequences of all four NF1-like proteins (NF1/Red1, NF1/L, NF1/X, and NF1/CTF), which are virtually identical, contain the DNA-binding domain that recognizes TGG. Functional diversity may arise from differences in the COOH-terminal sequences. We hypothesize that the COOH-terminal domain interacts with adjacent DNA-binding proteins, thereby stabilizing the binding of a particular NF1-like protein to a particular promoter. This protein-protein interaction confers specificity to a class of proteins whose DNA-recognition sequence is widespread in the genome. Sterols may repress transcription of the reductase gene by disrupting this protein-protein interaction.

Original languageEnglish (US)
Pages (from-to)8963-8967
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number23
DOIs
StatePublished - Jan 1 1988

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NFI Transcription Factors
Oxidoreductases
Genes
Proteins
Cricetinae
Staphylococcal Protein A
DNA-Binding Proteins
3-hydroxy-3-methylglutaryl-coenzyme A
Complementary DNA
Genome
Peptides
Sterols

ASJC Scopus subject areas

  • General

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Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. / Gil, G.; Smith, J. R.; Goldstein, J. L.; Slaughter, Clive A.; Orth, K.; Brown, M. S.; Osborn, T. F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 23, 01.01.1988, p. 8963-8967.

Research output: Contribution to journalArticle

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abstract = "DNA-binding proteins of the nuclear factor 1 (NF1) family recognize sequences containing TGG. Two of these proteins, termed reductase promoter factor (RPF) proteins A and B, bind to the promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a negatively regulated enzyme in cholesterol biosynthesis. In the current study, we determined the sequences of peptides derived from hamster RPF proteins A and B and used this information to isolate a cDNA, designated pNF1/Red1, that encodes RPF protein B. The peptide sequence of RPF protein A, the other reductase-related protein, suggests that it is the hamster equivalent of NF1/L, which was previously cloned from rat liver. We also isolated a hamster cDNA for an additional member of the NF1 family, designated NF1/X. Thus, the hamster genome contains at least three genes for NF1-like proteins. It is likely to contain a fourth gene, corresponding to NF1/CTF, which was previously cloned from the human. The NH2-terminal sequences of all four NF1-like proteins (NF1/Red1, NF1/L, NF1/X, and NF1/CTF), which are virtually identical, contain the DNA-binding domain that recognizes TGG. Functional diversity may arise from differences in the COOH-terminal sequences. We hypothesize that the COOH-terminal domain interacts with adjacent DNA-binding proteins, thereby stabilizing the binding of a particular NF1-like protein to a particular promoter. This protein-protein interaction confers specificity to a class of proteins whose DNA-recognition sequence is widespread in the genome. Sterols may repress transcription of the reductase gene by disrupting this protein-protein interaction.",
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