title: Transcription factor-recognition sequences potentially involved in modulation of gene expression after exposure to low-dose-rate γ-rays in the mouse liver.
abstract: In vivo modulation of gene expression profiles after low-dose and low-dose-rate irradiation has been observed in a variety of experimental systems. However, few studies actually investigated the underlying mechanisms for these genetic responses. In this study, we used pre-existing microarray data and searched for gene modulations in response to long-term, low-dose-rate irradiation. Nucleotide sequences in the neighboring region of the up-regulated, down-regulated, and unaffected genes were retrieved from the Entrez Gene database, and recognition sequences for transcription factors (TFs) were searched using the TFSEARCH database. As a result, we suggested 21 potential TF-binding sites with significantly different incidence between the three gene groups (up-regulated, down-regulated and unaffected gene groups). The binding sites for sterol regulatory element-binding protein 1 (SREBP-1), aryl hydrocarbon receptor (AhR/Ar) and olfactory 1 (Olf-1) were suggested to be involved in up-regulation, while the binding sites for glucocorticoid receptor (GR(GGTACAANNT GTYCTK) ) and hepatocyte nuclear factor 1 (HNF-1) were suggested to be involved in down-regulation of the genes. In addition, the binding sites for activating enhancer-binding protein 4 (AP-4), nuclear factor-κB (NFκB), GR (NNNNNNCNNTNTGTNCTNN) and early growth response 3 (Egr-3) were correlated with modulation of gene expression regardless of the direction of modulation. Our results suggest that these TF-binding sites are involved in gene modulations after long-term continuous irradiation with low-dose-rate γ rays. GR and/or SREBP-1 might be associated with the altered metabolic process observed in liver after exposure to low-dose-rate irradiation.
authors.affiliation: Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vares
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Uehara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakajima
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Keiko
authors.initials: K
authors.lastname: Taki
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oghiso
authors.forename: Kimio
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ichinohe
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nenoi
mesh_terms: D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D051776:Early Growth Response Protein 3 / Q000378:metabolism; D005720:Gamma Rays; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C497369:Egr3 protein, mouse; D016328:NF-kappa B; D018336:Receptors, Aryl Hydrocarbon; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C055473:enhancer-binding protein AP-4; D051776:Early Growth Response Protein 3