Torsional behavior of chromatin is modulated by rotational phasing of nucleosomes.
Bottom Line: Torsionally stressed DNA plays a critical role in genome organization and regulation.While the effects of torsional stresses on naked DNA have been well studied, little is known about how these stresses propagate within chromatin and affect its organization.The observed behavior is shown to arise from an interplay between nucleosomal transitions into states with crossed and open linker DNAs and global supercoiling of arrays into left- and right-handed coils, where Ψ0 serves to modulate the energy landscape of nucleosomal states.
Affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA.Show MeSH
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Mentions: Before applying twist, we obtain the 0.34 pN tension-equilibrated conformations of nucleosome arrays as a function of the phase angle Ψ0. We first determine, using the procedure described in Supplementary Text and Supplementary Figure S1c, the fractions fO, fN and fP of nucleosomes in the array with open, negatively- and positively-crossed linker DNAs, respectively (Figure 2a). We refer to these states as open, negative and positive. The arrays are composed of mostly negative and open nucleosomes for all Ψ0, but their relative population varies strongly with Ψ0. When Ψ0 = 0, the nucleosomes are distributed almost evenly between open and negative states, consistent with recent FRET measurements (35). The nucleosomal DNA entry/exit angle of 120°, fixed in our model according to the nucleosome crystal structure, along with electrostatic repulsion between the entering and exiting linker DNAs likely promotes such a distribution. When Ψ0 < 0, the open state becomes more prevalent. In this case, the DNA pitch increases as the DNA is undertwisted. Consequently, the ‘downstream’ nucleosomes are oriented anticlockwise relative to the ones ‘upstream’, causing the two linkers DNAs to diverge (Figure 1a). When Ψ0 > 0, the negatively-crossed state becomes dominant. Here, the DNA pitch decreases as the DNA is overtwisted, leading to clockwise rotation of the downstream nucleosome, and subsequent convergence of the linker DNAs (Figure 1c).
Affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA.