Hydrogen peroxide induces Sp1 methylation and thereby suppresses cyclin B1 via recruitment of Suv39H1 and HDAC1 in cancer cells

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26 引文 斯高帕斯(Scopus)

摘要

Sp1 is an important transcription factor for a number of genes that regulate cell growth and survival. Sp1 is an anchor protein that recruits other factors to regulate its target genes positively or negatively, but the mechanism of its functional switch by which positive or negative coregulators are recruited is not clear. In this study, we found that Sp1 could be methylated and that methylation was maintained by treatment with pargyline, a lysine-specific demethylase 1 (LSD1) inhibitor or knock LSD1 down directly. Hydrogen peroxide treatment increased the methylation of Sp1 and repressed Sp1 transcriptional activity. Investigation of the mechanism by which methylation decreased Sp1 activity found that methylation of Sp1 increased the recruitment of Su(var) 3-9 homologue 1(Suv39H1) and histone deacetylase 1 (HDAC1) to the cyclin B1 promoter, resulting in deacetylation and methylation of histone H3 and subsequent downregulation of cyclin B1. Finally, downregulation of cyclin B1 led to cell cycle arrest at the G2 phase. These results show that methylation of Sp1 causes it to act as a negative regulator by recruiting Suv39H1 and HDAC1 to induce chromatin remodeling. This finding that methylation acts as a functional switch provides new insight into the modulation of Sp1 transcriptional activity.
原文英語
頁(從 - 到)2309-2318
頁數10
期刊Free Radical Biology and Medicine
51
發行號12
DOIs
出版狀態已發佈 - 十二月 15 2011

ASJC Scopus subject areas

  • 生物化學
  • 生理學(醫學)

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