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Chromatin remodeling plays a crucial role in the activation or repression of transcription of eukaryotic genes. The chromatin remodeler ACF acts as a dimeric, processive motor to evenly space nucleosomes, favoring repression of gene transcription. Single-molecule experiments have established that ACF moves the nucleosome more efficiently towards the longer flanking DNA than towards the shorter flanking DNA, thereby centering an initially ill-positioned nucleosome on DNA substrates. In this paper we present a one-motor model with nucleosomal repositioning rates dependent on the DNA flanking length. The corresponding master equation is solved analytically with experimentally relevant parameter values. The velocity profile and the effective diffusion constant for nucleosome sliding, computed from the probability distributions, are in accordance with available experimental data. In order to address the observed kinetic pauses in experimental Förster Resonance Energy Transfer profiles, we extend the master equation to account for transitions between explicit motor states, i.e., adenosine triphosphate (ATP) loading and ATP hydrolysis in both ACF motors. The results of this extended two-motor model are compared to the previous effective one-motor model and allow insights into the role of the synchronization of the two motors acting on the nucleosome.

Citation

Yves Vandecan, Ralf Blossey. Stochastic description of single nucleosome repositioning by ACF remodelers. Physical review. E, Statistical, nonlinear, and soft matter physics. 2012 Jun;85(6 Pt 1):061920

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PMID: 23005140

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