Epigenetic silencing of CCAAT/enhancer-binding protein δ activity by YY1/polycomb group/DNA methyltransferase complex

Chiung Yuan Ko, Hey Chi Hsu, Meng Ru Shen, Wen Chang Chang, Ju Ming Wang

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Human CCAAT/enhancer-binding protein δ (CEBPD) has been reported as a tumor suppressor because it both induces growth arrest involved in differentiation and plays a crucial role as a regulator of pro-apoptotic gene expression. In this study, CEBPD gene expression is down-regulated, and "loss of function" alterations in CEBPD gene expression are observed in cervical cancer and hepatocellular carcinoma. Suppressor of zeste 12 (SUZ12), a component of the polycomb repressive complex 2 (PRC2), silences CEBPD promoter activity, enhancing the methylation of exogenous CEBPD promoter through the proximal CpG islands. Moreover, this molecular approach is consistent with the opposite mRNA expression pattern between SUZ12 and CEBPD in cervical cancer and hepatocellular carcinoma patients.Wefurther demonstrated that Yin-Yang-1 (YY1) physically interacts with SUZ12 and can act as a mediator to recruit the polycomb group proteins and DNA methyltransferases to participate in the CEBPD gene silencing process. Taking these results into consideration, we not only demonstrate the advantage of SUZ12-silenced CEBPD expression in tumor formation but also clarify an in vivo evidence for YY1-mediated silencing paths of SUZ12 and DNA methyltransferases on the CEBPD promoter.

Original languageEnglish
Pages (from-to)30919-30932
Number of pages14
JournalJournal of Biological Chemistry
Volume283
Issue number45
DOIs
Publication statusPublished - 2008 Nov 7

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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