Transcription Factor NF-κB Unravels Nucleosomes

Abstract

NF-{kappa}B is a transcription factor responsible for activating hundreds of genes in mammalian organisms. To accomplish its function, NF-{kappa}B 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. Mapping of the nucleosomes did not reveal displacement of under-wrapped nucleosomes from their original position, suggesting that unravelling involves dissociation of one or both flanks of the nucleosomes. We discovered two binding modes of NF-{kappa}B associated with nucleosome unraveling - NF-{kappa}B bound to the nucleosome core and to the DNA flanks and propose models explaining the interaction of NF-{kappa}B with the nucleosome. We speculate that NF-{kappa}B can function as a pioneer factor enhancing its ability to facilitate rapid transcriptional response to cell stress.