Transcription factor NF-κB unravels nucleosomes

NF-kappa B is a transcription factor responsible for activating hundreds of genes in mammalian organisms. To accomplish its function, NF-KB must interact with DNA occupied by nucleosomes, but how this interaction occurs is unclear. Here we used Atomic Force Microscopy to characterize complexes of NF-kappa B with nucleosomes assembled on different DNA templates. The assembly of NF-kappa B-nucleosome complexes leads to a substantial decrease of DNA wrapping efficiency from 149 +/- 2 bp (SEM) for the control nucleosome sample to 135 +/- 3 bp for complexes of nucleosomes with NF-kappa B. Mapping of the nucleosomes did not reveal displacement of underwrapped nucleosomes from their original position, suggesting that unravelling involves dissociation of one or both flanks of the nucleosomes. Binding of NF-kappa B to the core was identified by nucleosome core volume measurements. We discovered two binding modes of NF-kappa B associated with nucleosome unravelling - NF-kappa B bound to the nucleosome core and to the DNA flanks. From these findings we propose two models explaining the interaction of NF-kappa B with the nucleosome complex. The partial unravelling of nucleosomes by NF-kappa B makes the DNA segment at the edge of the nucleosome core accessible, facilitating the transcription process. We speculate that NF-kappa B can function as a pioneer factor, enhancing its ability to facilitate rapid transcriptional response to cell stress.