SWI/SNF Has Intrinsic Nucleosome Disassembly Activity that Is Dependent on Adjacent Nucleosomes

Abstract

SUMMARY The ATP-dependent chromatin remodeling complex SWI/SNF regulates transcription and has been implicated in promoter nucleosome eviction. Efficient nucleosome disassembly by SWI/SNF alone in biochemical assays has however not been directly observed. Employing a model system of dinucleosomes rather than mononucleosomes, we demonstrate that remodeling leads to ordered and efficient disassembly of one of the two nucleosomes. An H2A/H2B dimer is first rapidly displaced and then in a slower reaction an entire histone octamer is lost. Nucleosome disassembly by SWI/SNF did not require additional factors such as chaperones or acceptors of histones. Observations in single molecules as well as bulk measurement suggest that a key intermediate in this process is one in which a nucleosome is moved towards the adjacent nucleosome. SWI/SNF recruited by the transcriptional activator Gal4-VP16 preferentially mobilizes the proximal nucleosome and destabilizes the adjacent nucleosome.

The INO80 ATP-Dependent Chromatin Remodeling Complex Is a Nucleosome Spacing Factor

“…Our study delineates the intrinsic differences between INO80 and SWI/SNF and points to how they may increase accessibility of chromatinized DNA in distinct ways. SWI/SNF has been shown recently to have nucleosome disassembly activity with di-and trinucleosome substrates that are similar to those used in this study (10). The disassembly activity of SWI/SNF is independent of any histone chaperone or DNA acceptor cofactor.…”

p53 binding to nucleosomes within the p21 promoter in vivo leads to nucleosome loss and transcriptional activation

“…Conceivably partial loss of a portion of the histones from that nucleosome and/or a subsequent clash between two neighboring nucleosomes has occurred. This is not unheard of-see, for example, Dechassa et al (23). Using in vitro reconstituted mono-, di-, and three-nucleosome arrays in the presence of SWI/SNF, those authors demonstrated collision of two neighboring nucleosomes, as well as partial loss of H2A/H2B dimer.…”

Nucleosome Remodeling and Epigenetics

“…An interesting variation of the theme has been suggested, whereby a nucleosome is used as a "wedge" to destabilize an adjacent particle. If nucleosomes are moved to collide with one another, DNA may be peeled off one or both of them, yielding unconventional remodeling intermediates (Chaban et al 2008;Engeholm et al 2009;Dechassa et al 2010). This possibility is consistent with the fact that RSC engulfs the nucleosome to which it is bound (Fig.…”