Subset of genes targeted by transcription factor NF-κB in TNFα-stimulated human HeLa cells

Abstract

Nuclear factor κB (NF-κB) is a ubiquitous transcription factor that plays a pivotal role in controlling important cellular processes, ranging from normal cell growth and differentiation to apoptosis and cancer. In recent years, many new target genes of NF-κB have been identified in several cell lines that were treated with various stimuli using chromatin immunoprecipitation (ChIP)-based high-throughput techniques. However, the target genes from various cell lines and stimuli are not identical, and many of them are cell or stimulus specific. This suggests that it is necessary to investigate different cell lines and stimuli for identifying all target genes of this transcription factor. In this study, the direct target genes (DTGs) of NF-κB in the TNFα-stimulated HeLa cells were identify by using ChIP-Seq, RNAi, and gene expression profiling techniques. As a result, 584 DTGs were identified, in which 266 were activated and 318 were repressed. The κB motif searching revealed that 50% of these genes contained canonical κB sites in their ChIP peaks and 90% contained non-canonical κB sites in their ChIP peaks. In comparison with target genes identified in LPS-treated U937 and THP-1, only limited numbers (10∼23) of target genes were shared by each of two cell lines, and only two gene (NFKB2 and STAT5A) were commonly shared by three cell lines.