原创力文档comprehensive study in the inhibitory effect of berberine on gene transcription, including tata box全面研究小檗碱抑制作用的基因转录,包括塔塔盒子.pdfVIP
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comprehensive study in the inhibitory effect of berberine on gene transcription, including tata box全面研究小檗碱抑制作用的基因转录,包括塔塔盒子
Comprehensive Study in the Inhibitory Effect of
Berberine on Gene Transcription, Including TATA Box
1. 1,2. 1 1 1 1 1
Yugang Wang , Michael M. Kheir , Yushuang Chai , Jun Hu , Dongming Xing , Fan Lei *, Lijun Du *
1 Protein Science Laboratory of the Ministry of Education, Laboratory of Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University,
Beijing, China, 2 Department of Chemistry, University of Michigan, Ann Arbor, Michigan, United States of America
Abstract
Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently
there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the
relationship between BBR’s association with DNA and the function of DNA. Here we report that the distribution of BBR
within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus
peaks at around 4 mmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin
was altered immediately after their association with BBR. Moreover, this association can effectively suppress the
transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated
further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and
this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we
hypothesize that berberine can suppress the transcription of DNA i
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