Proteins binding to the liver-specific pyruvate kinase gene promoter. A unique combination of known factors.
A 183 base-pair fragment of the liver-specific promoter of the L-type puruvate kinase (L-PK) gene has been shown by transfection assay to be sufficient to confer a tissue-specific expression to a reporter gene. The proteins binding in vitro to this fragment have been investigated by a combination of DNase I footprinting, gel retardation of synthetic oligonucleotides and ultraviolet cross-linking. Four proteins from liver nuclear extracts bind to the investigated fragment. They were called, from 3' to 5', L1 to L4 binding factors. The L1 site (nucleotides -95 to -66 with respect to the cap site) binds hepatocyte nuclear factor 1 (HNF1), a liver-specific protein. The L2 site (nucleotides -114 to -97) binds the ubiquitous nuclear factor 1 (NF1), or a related factor. The L3 site (nucleotides -144 to -126) binds liver factor A1 (LF-A1), another liver-specific protein. Finally, the L4 site (nucleotides -168 to -145) binds major late transcription factor (MLTF/USF/UEF), an ubiquitous protein. Each of these proteins has been detected in other liver-specific promoters, but their combination is unique to the liver-specific promoter of the L-PK gene.
Vaulont
S
S
Unité de Recherches en Génétique et Pathologie Moléculaires, INSERM U. 129 CHU Cochin, Paris, France.
Puzenat
N
N
Levrat
F
F
Cognet
M
M
Kahn
A
A
Raymondjean
M
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D003851:Deoxyribonucleases / Q000032:analysis / Q000378:metabolism; D005796:Genes; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D009698:Nucleoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C051096:MLTF protein, adenovirus; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D009698:Nucleoproteins; D014157:Transcription Factors; D014764:Viral Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D011770:Pyruvate Kinase; D003851:Deoxyribonucleases