Abstract
The present studies have examined the effects of ionizing radiation on control of the early growth response 1 (EGR1) gene. Exposure of human HL-525 cells to x-rays was associated with increases in EGR1 mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGR1 gene transcription. Sequences responsive to ionizing radiation-induced signals were determined by deletion analysis of the EGR1 promoter. The results demonstrate that x-ray inducibility of the EGR1 gene is conferred by a region containing six serum response or CC(A+T-rich)6GG (CArG) motifs. Further analysis confirmed that the region encompassing the three distal or upstream CArG elements is functional in the x-ray response. Moreover, this region conferred x-ray inducibility to a minimal thymidine kinase gene promoter. Taken together, these results indicate that ionizing radiation induces EGR1 transcription through CArG elements.
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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Base Sequence
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Cell Nucleus / physiology*
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Chloramphenicol O-Acetyltransferase / genetics
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Chloramphenicol O-Acetyltransferase / metabolism
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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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Early Growth Response Protein 1
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Gene Conversion
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Gene Expression Regulation, Neoplastic / radiation effects*
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Humans
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Immediate-Early Proteins*
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Leukemia, Myeloid
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Promoter Regions, Genetic*
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RNA, Neoplasm / genetics
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RNA, Neoplasm / isolation & purification
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Recombinant Fusion Proteins / metabolism
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Simplexvirus / enzymology
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Simplexvirus / genetics
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Thymidine Kinase / genetics
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Thymidine Kinase / metabolism
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Transcription Factors / genetics*
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Transcription, Genetic / radiation effects*
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Tumor Cells, Cultured
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X-Rays
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Zinc Fingers / genetics
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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Immediate-Early Proteins
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Oligodeoxyribonucleotides
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RNA, Neoplasm
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Recombinant Fusion Proteins
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Transcription Factors
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Chloramphenicol O-Acetyltransferase
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Thymidine Kinase