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Identification and functional analysis of a CDE/CHR element in the POLD1 promoter

查看全文 作  者:SONG NanMeng1,ZHU XiaoYu1,2,SHI Lei1,AN Jing1,WU YanWei1 & SANG JianLi1 1 Key Laboratory of Cell Proliferation and Regulation of Ministry of Education,Beijing Normal University,Beijing 100875,China;2 State Key Laboratory for Infectious Disease Prevention and Control,Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China 高影响力作者 出  处:《Science China(Life Sciences)》索引2009年第52卷第6期,共9页高影响力期刊 基  金:Supported by National Basic Research Program of China (Grant No. 2007CB914401);National High Technology Research and Development Program of China (Grant No. 2006AA02Z4A6) 摘  要:DNA polymerase delta is encoded by the POLD1 gene,the transcription of which is strictly cell cycle-dependent.However,the means by which POLD1 transcription is regulated by the cell cycle mechanism is currently unknown.We discovered a novel element in the POLD1 promoter known as a CDE(cell cycle-dependent element)/CHR(cell cycle gene homology region) element.A series of luciferase reporter constructs containing various POLD1 promoter mutations were used to investigate the role of the CDE/CHR element in POLD1 transcription.When the CDE/CHR element was mutated,the promoter activity was up-regulated,and the cell-cycle related factors E2F1 and p21 stopped regulating the promoter.Furthermore,cell cycle-dependent changes in the promoter activity required the integrative CDE/CHR element.Electrophoretic mobility shift assay(EMSA) revealed the presence of at least three types of DNA/protein complexes binding to the CDE/CHR element.Our findings provide strong evidence that the CDE/CHR-like sequence is an active functional element in the POLD1 promoter,which is important for the cell cycle regulation of the POLD1 gene. 关 键 词:POLD1 GENE PROMOTER CDE/CHR ELEMENT SITE MUTANT
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