The rat hepatic leukemia factor (HLF) gene encodes two transcriptional activators with distinct circadian rhythms, tissue distributions and target preferences.
Hepatic leukemia factor (HLF) is a member of the PAR family of transcription regulatory proteins. We have characterized the rat HLF gene and studied its expression and activity. The rat HLF gene is transcribed from two alternative promoters, alpha and beta, with different circadian amplitudes and tissue specificities. The alpha RNA isoforms produce a 43 kDa protein, HLF43, abundant in brain, liver and kidney, like the previously described human HLF RNA. The beta RNA HLF isoforms use a CUG codon to initiate translation of a novel 36 kDa protein, HLF36, which is shorter at its N-terminus relative to the 43 kDa form. HLF36 is expressed uniquely in the liver, where it is the most abundant HLF protein. Surprisingly, the two proteins accumulate in the liver with different circadian amplitudes and have distinct liver-specific promoter preferences in transfection experiments. Thus, HLF43 stimulates transcription from the cholesterol 7 alpha-hydroxylase promoter much more efficiently than from the albumin promoter, while the converse is true for HLF36.
Falvey
E
E
Department of Molecular Biology, University of Geneva, Switzerland.
Fleury-Olela
F
F
Schibler
U
U
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm; D003062:Codon; D004252:DNA Mutational Analysis; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D050976:Basic-Leucine Zipper Transcription Factors; D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C490671:HLF protein, human; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C095828:Hlf protein, rat