DNA sequence-dependent contributions of core histone tails to nucleosome stability: Differential effects of acetylation and proteolytic tail removal

Modulation of nucleosome stability in chromatin plays an important role in eukaryotic gene expression. The core histone N-terminal tail domains are be lieved to modulate the stability of wrapping nucleosomal DNA and the stabil ity of the chromatin filament. We analyzed the contribution of the tail dom ains to the stability of nucleosomes containing selected DNA sequences that are intrinsically straight, curved, flexible, or inflexible. We find that the presence of the histone tail domains stabilizes nucleosomes containing DNA sequences that are intrinsically straight or curved. However, the tails do not significantly contribute to the free energy of nucleosome formation with flexible DNA. Interestingly, hyperacetylation of the core histone tai l domains does not recapitulate the effect of tail removal by limited prote olysis with regard to nucleosome stability. We find that acetylation of the tails has the same minor effect on nucleosome stability for all the select ed DNA sequences. A comparison of histone partitioning between long donor c hromatin, acceptor DNA, and free histones in solution shows that the core h istone tails mediate internucleosomal interactions within an H1-depleted ch romatin fiber amounting to an average free energy of about 1 kcal/mol. Thus , such interactions would be significant with regard to the free energies o f sequence-dependent nucleosome positioning. Last, we analyzed the contribu tion of the H2A/H2B dimers to nucleosome stability. We find that the intact nucleosome is stabilized by 900 cal/mol by the presence of the dimers rega rdless of sequence. The biological implications of these observations are d iscussed.