title: Ionizing radiation activates transcription of the EGR1 gene via CArG elements.
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.
authors.affiliation: Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: R
authors.initials: R
authors.lastname: Datta
authors.forename: E
authors.initials: E
authors.lastname: Rubin
authors.forename: V
authors.initials: V
authors.lastname: Sukhatme
authors.forename: S
authors.initials: S
authors.lastname: Qureshi
authors.forename: D
authors.initials: D
authors.lastname: Hallahan
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: D W
authors.initials: DW
authors.lastname: Kufe
mesh_terms: 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
chemical_list: 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