CEBPG regulates ERCC5/XPG expression in human bronchial epithelial cells and this regulation is modified by E2F1/YY1 interactions.
Marked inter-individual variation in lung cancer risk cannot be accounted for solely by cigarette smoke and other environmental exposures. Evidence suggests that variation in bronchial epithelial cell expression of key DNA repair genes plays a role. Variation in these genes correlates with variation in expression of CEBPG and E2F1 transcription factors. Here, we investigated the mechanistic basis for correlation of the DNA repair gene ERCC5 (previously known as XPG) with CEBPG and E2F1. CEBPG expression vector transfected into H23 or H460 cell lines up-regulated endogenous ERCC5 and also luciferase from a reporter construct containing 589 bp of ERCC5 5' regulatory region. A recognition site for CEBPG and a region containing sites for YY1 on the sense strand and E2F1 on the anti-sense strand participated in CEBPG up-regulation of ERCC5. CEBPG, E2F1 and YY1 binding to their respective sites were confirmed by electrophoretic mobility shift assay. Thus, we conclude that CEBPG regulates ERCC5 expression and this regulation is modified by E2F1/YY1 interactions. Several polymorphisms have been identified in these regions and, based on the data presented here, it is reasonable to hypothesize that they may contribute to risk for bronchogenic carcinoma.
Crawford
E L
EL
Department of Medicine, The University of Toledo, Toledo, OH 43614, USA.
Blomquist
T
T
Mullins
D N
DN
Yoon
Y
Y
Hernandez
D R
DR
Al-Bagdhadi
M
M
Ruiz
J
J
Hammersley
J
J
Willey
J C
JC
D001665:Binding Sites; D001980:Bronchi / Q000166:cytology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D004720:Endonucleases / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic; D020545:Respiratory Mucosa / Q000166:cytology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D050986:YY1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D000099250:DNA Excision Repair Protein ERCC-5
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D000099250:DNA Excision Repair Protein ERCC-5; C405462:CCAAT-enhancer-binding protein-gamma; C493753:E2F1 protein, human; C494698:YY1 protein, human