Enhancer activity of HS2 of the human beta-LCR is modulated by distance from the key nucleosome.

A class of curved DNA appears universally in eukaryotic genomic DNA at an average distance of approximately 680 bp and shows nucleosome positioning activity by having high affinity for histone core particles in an orientation- and position-dependent manner. Here, we report that the enhancer activity at DNase I hypersensitive site 2 (HS2) of the human beta-globin locus control region (beta-LCR) can be modulated by the curved DNA located at a distance of two nucleosomes from HS2 and that the nucleosome at the curved DNA regulates nearby nucleosome phases as a key nucleosome. Erythroid-specific nucleosome phases which caused deviation of the NF-E2 (p18-p45 dimer) binding site from the nucleosome dyad axis were over-represented when the distance between the key nucleosome and HS2 exceeded 80 bp longer than the original length. At this state, enhancer activity was approximately 50% of that in the original construct, presumably due to reduced binding of transcription factors.