Activation of the erythropoietin receptor promoter by transcription factor GATA-1.
Erythropoietin, a glycoprotein produced by the kidneys in response to anemia and hypoxia, is a major growth factor for cells of the erythroid lineage. Erythropoietin interacts with high-affinity cell surface receptors (EpoR) present on developing progenitors and is required for their survival. Previously we characterized the gene for EpoR and demonstrated that its promoter acts in a cell-specific manner. Here we show that the hematopoietic-specific transcription factor GATA-1 is necessary, and indeed is sufficient as the sole cell-restricted regulator, for activation of the EpoR promoter in fibroblast transfection assays. Hence, GATA-1, which participates in transcriptional control of the majority of erythroid-expressed genes, also acts on the promoter of an essential lineage-restricted receptor (EpoR). This central contribution of GATA-1 to EpoR promoter function provides a mechanism whereby a cell-restricted regulator may ensure the viability and subsequent maturation of progenitor cells during hematopoietic differentiation.
Zon
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LI
Division of Hematology-Oncology, Children's Hospital, Boston, MA.
Youssoufian
H
H
Mather
C
C
Lodish
H F
HF
Orkin
S H
SH
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin / Q000378:metabolism; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017467:Receptors, Erythropoietin; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D014157:Transcription Factors; D004921:Erythropoietin