The extinction of erythroid genes after tetradecanoylphorbol acetate treatment of erythroleukemic cells correlates with down-regulation of the tissue-specific factors NF-E1 and NF-E2.
We have studied the elements involved in the tetradecanoylphorbol acetate (TPA)-mediated extinction of erythroid-specific genes. We show that transcription driven by a -714/+78-base pair DNA fragment of the erythroid promoter of the human porphobilinogen deaminase gene is down-regulated upon TPA treatment of erythroleukemic cells. Examination of the DNA binding activity of trans-acting factors involved in the expression of the porphobilinogen deaminase erythroid promoter showed (i) a constitutive expression of the CACC binding proteins and (ii) a decrease in DNA binding activity of two tissue-specific factors, NF-E1 and NF-E2. Kinetics experiments indicated that NF-E2 was down-regulated after 1 h of TPA treatment whereas NF-E1 was down-regulated at the protein and mRNA levels only after 5 h of TPA treatment. These results suggest that different pathways, acting via different transcription factors, are involved in the TPA-mediated extinction of erythroid-specific genes.
Mignotte
V
V
Institut National de la Santé et de la Recherche Médicale U.91 (Centre National de la Recherche Scientifique UA 607), Hôpital Henri Mondor, Creteil, France.
Navarro
S
S
Eleouet
J F
JF
Zon
L I
LI
Romeo
P H
PH
D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014157:Transcription Factors; D011163:Hydroxymethylbilane Synthase; D013755:Tetradecanoylphorbol Acetate