Ionizing radiation activates transcription of the EGR1 gene via CArG elements.
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.
Datta
R
R
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Rubin
E
E
Sukhatme
V
V
Qureshi
S
S
Hallahan
D
D
Weichselbaum
R R
RR
Kufe
D W
DW
D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005785:Gene Conversion; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D017874:Immediate-Early Proteins; D007951:Leukemia, Myeloid; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D014965:X-Rays; D016335:Zinc Fingers / Q000235:genetics
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D009838:Oligodeoxyribonucleotides; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase