Role of Ets-1 in transcriptional regulation of transferrin receptor and erythroid differentiation.
High expression of transferrin receptor (TfR) on the membrane of erythroid cells accounts for the high level of iron required to sustain heme synthesis. Several studies indicate that during erythroid differentiation TfR expression is highly dependent on transcriptional regulation. In this study we characterized the minimal region able to confer transcriptional regulation during erythroid differentiation in Friend leukemia cells (FLC). This region of 120 bp, upstream the transcription start site, contains an overlapping consensus recognition sequence for AP1/CREB/ATF transcription factors and for proteins of the Ets family and a GC rich region. Here, we report that both the Ets and the Ap1/CRE like sites are essential for promoter activity during erythroid differentiation. We showed that Ets-1 binds to the EBS-TfR and its binding activity decreases in FLC induced to differentiate and during normal erythroid differentiation. Consistent with this, FLC constitutively expressing Ets-1 show a decrease in TfR gene expression, globin mRNA and hemoglobin synthesis. We conclude that Ets-1 binding activity is modulated during erythroid maturation and that a deregulated expression of this transcription factor interferes with terminal erythroid differentiation.
Marziali
Giovanna
G
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Perrotti
Edvige
E
Ilari
Ramona
R
Lulli
Valentina
V
Coccia
Eliana M
EM
Moret
Rémy
R
Kühn
Lukas C
LC
Testa
Ugo
U
Battistini
Angela
A
D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA; D004912:Erythrocytes / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D011990:Receptors, Transferrin / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011990:Receptors, Transferrin; D014157:Transcription Factors; D004247:DNA