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

M Dandrea, M Donadelli, C Costanzo… - Nucleic acids …, 2009 - academic.oup.com
M Dandrea, M Donadelli, C Costanzo, A Scarpa, M Palmieri
Nucleic acids research, 2009academic.oup.com
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-α, 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 …
Abstract
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-α, 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.
Oxford University Press