Nucleosome Dynamics

DNA wrapped around a histone octamer can be blocked from interactions with proteins essential for transcription, replication and other nuclear processes. Exposure of regulatory elements within DNA can occur either by sliding of nucleosomes, to position these sequences within linker DNA, or by transitionally lifting the DNA molecule off the nucleosome (Fig. 5.2). The first process is actively regulated by chromatin remodeling complexes, while the second process occurs passively in solution and is termed nucleosome dynamics. Sliding of the nucleosome across DNA does not occur without the aid of enzymes because the energy-of-activation barrier is prohibitively high, due to numerous hydrogen and electrostatic interactions that anchor the nucleosome in place. DNA positioned near the border of the nucleosome could partially unwrap and then rebind further upstream, leading to a bulge at the opposite side of the nucleosome (Kassabov et al., 2003). Recently, the method of fluorescence resonance energy transfer (FRET) analysis was used to assign an equilibrium constant of approximately .05 for unwrapping the first few base pairs of DNA (at the entry/exit sites)

from the histories oetamer. Thus, at any given time ~5% of nucleosomes on average are partially unwrapped or breathing (Li and Widom, 2004). Additional kinetic experiments reveal that the rate constant for unwrapping is 4 s"1, while rewrapping occurs much faster at 20-90 s"1 (Li et al., 2005). Integration of these data with equilibrium constants and rate constants of DNA-binding proteins reveals a model where proteins have a window of opportunity to bind their sequences during its brief exposure thus preventing rewrapping of the DNA back onto the nucleosome. Physiologically, active cellular processes, such as DNA replication and chromatin remodeling, may widen or close this window of opportunity.

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