GSE55105
The NF-kB genomic landscape in lymphoblastoid B-cells
The nuclear factor kB (NF-kB) subunits RelA, RelB, c-Rel, p50 and p52 are each critical for B-cell development and function.  To systematically characterize their responses to canonical and non-canonical NF-kB pathways activity, we performed ChIP-seq analysis in lymphoblastoid B-cells. We found a surprisingly complex NF-kB binding landscape, which did not readily reflect the two NF-kB pathway paradigm.  Instead, ten subunit binding patterns were observed at promoters and eleven at enhancers.  Surprisingly, nearly one-third of NF-kB binding sites lacked kB motifs. De novo motif finding uncovered distinct modes of NF-kB recruitment at these sites. The oncogenic forkhead box protein FOXM1 and NF-kB co-occupied many kB sites despite the absence of a FOXM1 DNA motif.  FoxM1 knockdown decreased expression of key NF-kB targets and caused apoptosis.  Our study highlights opportunities for selective therapeutic NF-kB blockade. Overall design: ChIP-seq was used to define the genomic landscape of NF-kB DNA binding in lymphoblastoid cells. The raw data for GSM2628089 are not available.