Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites

Posttranslational acetylation of the conserved core histone N-terminal tail domains is linked to gene activation, but the molecular mechanisms involve d are not known. In an earlier study we showed that removing the tail domai ns altogether by trypsin proteolysis (which leaves nucleosomes nevertheless intact) leads to 1.5 to 14-fold increases in the dynamic equilibrium acces sibility of nucleosomal DNA target sites. These observations suggested that , by modestly increasing the equilibrium accessibility of buried DNA target sites, histone acetylation could result in an increased occupancy by regul atory proteins, ultimately increasing the probability of transcription init iation. Here, we extend these observations to a more natural system involvi ng intact but hyperacetylated nucleosomes. We find that histone hyperacetyl ation leads to 1.1 to 1.8-fold increases in position-dependent equilibrium constants for exposure of nucleosomal DNA target sites, with an average inc rease of 1.4(+/-0.1)-fold. The mechanistic and biological implications of t hese results are discussed. (C) 2001 Academic Press.