Context-specific regulation of LINE-1

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 12; no. 10; pp. 1101 - 1110
• Main Authors: Teneng, Ivo, Stribinskis, Vilius, Ramos, Kenneth S
• Format: Journal Article
• Language: English
• Published: Malden, USA Malden, USA : Blackwell Publishing Inc 01.10.2007; Blackwell Publishing Inc
• Subjects: Animals; Benzo(a)pyrene - chemistry; Cell Line; Endothelial Cells - cytology; Gene Expression Regulation; HeLa Cells; Humans; Ligands; Long Interspersed Nucleotide Elements - genetics; Long Interspersed Nucleotide Elements - physiology; Mice; Models, Biological; Myocytes, Smooth Muscle - cytology; Oxidative Stress; Polychlorinated Dibenzodioxins - pharmacology; Promoter Regions, Genetic; Transcriptional Activation; Ultraviolet Rays
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/j.1365-2443.2007.01117.x

The present study was conducted to evaluate the contextual specificity of long interspersed nuclear element-1 (LINE-1 or L1) activation by cellular stress and the role of the aryl hydrocarbon receptor (AHR) transcription factor and oxidative stress in the gene activation response. Activation of the AHR by the genotoxic carcinogen benzo(a)pyrene (BaP) increased L1 expression in human cervical carcinoma (HeLa) cells, human microvascular endothelial cells (HMEC), mouse vascular smooth muscle cells (mVSMC) and mouse embryonic kidney cells (mK4). In contrast, challenge with a different AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or UV irradiation (10-20 J/m²), induced L1 only in HeLa cells. Transactivation of the mouse L1Md-A5 promoter was observed in all cell types challenged with BaP, while TCDD was without effect, and UV only activated L1 in HeLa cells. Genetic and pharmacological experiments implicated the AHR and oxidative stress as contextual determinants of L1 inducibility by cellular stress.