Selective repression of YKL-40 by NF-κB in glioma cell lines involves recruitment of histone deacetylase-1 and -2

Here we show that in contrast to other cancer types, tumor necrosis factor (TNF)-α suppresses YKL-40 expression in glioma cell lines in a nuclear factor κB (NF-κB) dependent manner. Even though TNF-α causes recruitment of p65 and p50 subunits of NF-κB to the YKL-40 promoter in all cell types, recruitment of histone deacetylases (HDAC)-1 and -2, and a consequent deacetylation of histone H3 at the YKL-40 promoter occurs only in glioma cells. Importantly, using chromatin immunoprecipitation assays in frozen glioblastoma multiforme tissues, we show that YKL-40 levels decrease consistent with HDAC1 recruitment despite high levels of nuclear p-p65. This study presents a paradigm for NF-κB regulation of one of its targets in a strict cell type specific manner.