J. Yao et al., TWIST CONSTRAINTS ON LINKER DNA IN THE 30-NM CHROMATIN FIBER - IMPLICATIONS FOR NUCLEOSOME PHASING, Proceedings of the National Academy of Sciences of the United Statesof America, 90(20), 1993, pp. 9364-9368
Previous work has shown that nucleosome repeat lengths, and hence link
er DNA lengths, are preferentially quantized to a set of values differ
ing by integral multiples of the helical twist of DNA. An explanation
was proposed in which this preferential quantization is due to twist c
onstraints on linker DNA arising from nucleosome-nucleosome interactio
ns in folded chromatin. Here we report the results of a study, using e
thidium intercalation, designed to test whether twist constraints do i
ndeed exist. Electron microscopy reveals that ethidium intercalation c
auses decondensation of dinucleosomes. Direct measurement of the free
energy of intercalation by fluorescence spectroscopy reveals competiti
on between chromatin folding and ethidium intercalation. Results from
other laboratories establish that these effects of ethidium are due to
ethidium-induced changes in the twist of linker DNA, and not to a var
iety of other possible effects. We conclude that twist constraints on
linker DNA do exist. These may explain the observation of preferential
ly quantized linker DNA lengths. Implications of these results for mec
hanisms of nucleosome phasing and the mechanisms of drug action are di
scussed.