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

Abstract

A class of curved DNA appears universally in eukaryotic genomic DNA at an average distance of ∼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 β-globin locus control region (β-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 ∼50% of that in the original construct, presumably due to reduced binding of transcription factors.