Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
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.
Gil
G
G
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Smith
J R
JR
Goldstein
J L
JL
Slaughter
C A
CA
Orth
K
K
Brown
M S
MS
Osborne
T F
TF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008647:Mesocricetus; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D014157:Transcription Factors; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D006903:Hydroxymethylglutaryl CoA Reductases