MeCP2/H3meK9 are involved in IL-6 gene silencing in pancreatic adenocarcinoma cell lines

被引：50

作者：

Dandrea, Mario ^{[1
,2
]}

Donadelli, Massimo ^{[1
]}

Costanzo, Chiara ^{[1
]}

Scarpa, Aldo ^{[2
]}

Palmieri, Marta ^{[1
]}

机构：

[1] Univ Verona, Biochem Sect, Dept Morphol & Biomed Sci, I-37100 Verona, Italy

[2] Univ Verona, Dept Pathol, I-37100 Verona, Italy

来源：

NUCLEIC ACIDS RESEARCH | 2009年 / 37卷 / 20期

关键词：

BINDING PROTEIN MECP2; TUMOR-NECROSIS-FACTOR; KAPPA-B SITE; TRANSCRIPTIONAL REPRESSOR; INTERLEUKIN-6; PROMOTER; DNA METHYLATION; EXPRESSION; MECHANISMS; CANCER; CBF1;

D O I：

10.1093/nar/gkp723

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The aim of the present study was to analyse the molecular mechanisms involved in the Interleukin-6 (IL-6) silencing in pancreatic adenocarcinoma cell lines. Our results demonstrate that TNF-alpha, a major IL-6 inducer, is able to induce IL-6 only in three out of six cell lines examined. 5-aza-2'-deoxycytidine (DAC), but not trichostatin A (TSA), activates the expression of IL-6 in all cell lines, indicating that DNA methylation, but not histone deacetylation, plays an essential role in IL-6 silencing. Indeed, the IL-6 upstream region shows a methylation status that correlates with IL-6 expression and binds MeCP2 and H3meK9 only in the non-expressing cell lines. Our results suggest that critical methylations located from positions -666 to -426 relative to the transcription start site of IL-6 may act as binding sites for MeCP2.

引用

页码：6681 / 6690

页数：10

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