Cryo-EM structure of the nucleosome containing the enhancer DNA sequence.

Pioneer transcription factors specifically target their recognition DNA sequences within nucleosomes. FoxA is the pioneer transcription factor that binds to the gene enhancer in liver precursor cells, and is required for liver differentiation in embryos. The enhancer DNA sequence is reportedly incorporated into nucleosomes in cells, although the nucleosome structure containing the targeting sites for FoxA has not been clarified yet. In this study, we determined the nucleosome structure containing the enhancer (N1) sequence, by cryogenic electron microscopy at 4.0 Å resolution. The nucleosome structure with the enhancer DNA is not significantly different from the previously reported nucleosome structure with the Widom 601 DNA. Interestingly, in the nucleosomes, the enhancer DNA contains local flexible regions, as compared to the Widom 601 DNA. Consistently, DNaseI treatments revealed that, in the nucleosome, the enhancer (N1) DNA is more accessible than the Widom 601 sequence. The histones also associated less strongly with the enhancer (N1) DNA than the Widom 601 DNA in the nucleosome. Therefore, the local histone-DNA contacts may be responsible for the enhanced DNA accessibility in the nucleosome with the enhancer DNA.