Abstract
We have isolated cDNA clones of myeloid differentiation primary response (MyD) genes, activated in the absence of de novo protein synthesis following induction for differentiation along either the macrophage or granulocyte lineage in human myeloblastic leukemia HL-60 cells. One cDNA clone of a primary response gene, expressed upon macrophage differentiation, encoded for Egr-1, a zinc finger transcription factor. The Egr-1 gene was observed to be transcriptionally silent in HL-60 cells, but active in U-937 and M1 cells, the latter two being predetermined for macrophage differentiation. Egr-1 antisense oligomers in the culture media blocked macrophage differentiation in both myeloid leukemia cell lines and normal myeloblasts. HL-60 cells constitutively expressing an Egr-1 transgene (HL-60Egr-1) could be induced for macrophage, but not granulocyte, differentiation. These observations indicate that expression of Egr-1 is essential for and restricts differentiation of myeloblasts along the macrophage lineage.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Binding Sites
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Bone Marrow / physiology
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Bone Marrow Cells
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Nucleus / physiology
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DNA, Neoplasm / genetics
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DNA, Neoplasm / isolation & purification
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Dimethyl Sulfoxide / pharmacology
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Early Growth Response Protein 1
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Gene Expression
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Granulocytes / cytology
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Granulocytes / physiology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / physiology
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Humans
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Immediate-Early Proteins*
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Leukemia, Promyelocytic, Acute
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Macrophages / cytology*
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Macrophages / drug effects
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Macrophages / physiology
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Mice
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Mice, Inbred Strains
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Molecular Sequence Data
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Oligonucleotides, Antisense / pharmacology
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Poly A / genetics
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RNA / genetics
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RNA, Messenger
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
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Transfection
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Tumor Cells, Cultured
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Zinc Fingers / genetics
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Zinc Fingers / physiology*
Substances
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DNA, Neoplasm
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DNA-Binding Proteins
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EGR1 protein, human
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Early Growth Response Protein 1
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Egr1 protein, mouse
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Immediate-Early Proteins
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Oligonucleotides, Antisense
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RNA, Messenger
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Transcription Factors
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Poly A
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RNA
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Tetradecanoylphorbol Acetate
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Dimethyl Sulfoxide