Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene.
Two cis-acting sequences, recognized by two erythroid-specific trans-acting factors, are involved in the regulation of the erythroid promoter of the human gene coding for porphobilinogen deaminase (PBGD). The first region, located at -70, binds the erythroid factor NF-E1, and point mutations within this region abolish the induction of transcription of this promoter during murine erythroleukemia (MEL) cell differentiation. The second region, located at -160, binds the erythroid-specific factor NF-E2 and the ubiquitous factor AP1. Using UV cross-linking, we show that NF-E2 has a higher molecular weight than AP1, demonstrating that NF-E2 is not an erythroid-specific degradation product of AP1. By point mutagenesis of the NF-E2/AP1 binding site, we define mutations that abolish binding of either NF-E2 alone or AP1 and NF-E2 together. Regulation of transcription of the PBGD erythroid promoter is abolished by those mutations, suggesting that NF-E2 but not AP1 is necessary for correct regulation of this promoter in erythroid cells.
Institut National de la Santé et de la Recherche Médicale U.91, Hôpital Henri Mondor, Créteil, France.
V
V
Mignotte
J F
JF
Eleouet
N
N
Raich
P H
PH
Romeo
D000642:Ammonia-Lyases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D005796:Genes; D005809:Genes, Regulator; D005822:Genetic Vectors; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D015345:Oligonucleotide Probes; D011163:Hydroxymethylbilane Synthase; D000642:Ammonia-Lyases