The prenucleosome, a stable conformational isomer of the nucleosome

Abstract

Chromatin comprises nucleosomes as well as nonnucleosomal histone–DNA particles. Prenucleosomes are rapidly formed histone–DNA particles that can be converted into canonical nucleosomes by a motor protein such as ACF. Here we show that the prenucleosome is a stable conformational isomer of the nucleosome. It consists of a histone octamer associated with ∼80 base pair (bp) of DNA, which is located at a position that corresponds to the central 80 bp of a nucleosome core particle. Monomeric prenucleosomes with free flanking DNA do not spontaneously fold into nucleosomes but can be converted into canonical nucleosomes by an ATP-driven motor protein such as ACF or Chd1. In addition, histone H3K56, which is located at the DNA entry and exit points of a canonical nucleosome, is specifically acetylated by p300 in prenucleosomes relative to nucleosomes. Prenucleosomes assembled in vitro exhibit properties that are strikingly similar to those of nonnucleosomal histone–DNA particles in the upstream region of active promoters in vivo. These findings suggest that the prenucleosome, the only known stable conformational isomer of the nucleosome, is related to nonnucleosomal histone–DNA species in the cell.

Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler

“…Indeed, in the absence of other protein factors, the canonical nucleosome conformation observed in crystal structures appears to be the most highly populated conformation in solution (56). At the same time, the possibility of alternative nucleosome conformations during nucleosome assembly and transcription has also been raised (57,58). Our results provide additional evidence that the octamer adopts more than one conformation and further demonstrate that octamer distortability is functionally relevant.…”

CHD Chromatin Remodeling Protein Diversification Yields Novel Clades and Domains Absent in Classic Model Organisms

“…Moreover, recombinant AtPKL promotes prenucleosome maturation in addition to nucleosome mobilization ( Ho et al 2013 ; Carter et al 2018 ). These in vitro activities suggest that AtPKL, a subfamily II remodeler, contributes to nucleosome assembly as well as mobility, biochemical properties previously associated only with CHD remodelers in subfamily I ( Lusser et al 2005 ; Fei et al 2015 ). In addition, phylogenetic analyses suggest the existence of novel plant clades of CHD remodelers in subfamilies II and III that are absent in A. thaliana , raising the prospect of novel remodeling activities/roles for CHD proteins in this kingdom ( Hu et al 2013 ; Koster et al 2015 ).…”

The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes

“…We then cross-linked our chromatinized samples and several control samples with trimethylpsoralen, digested protein, and performed metal-shadowing electron microscopy to assess nucleosome occupancy along the DNA molecules across our conditions (Fig. 5b, c ) 55 , 56 . In these experiments, the presence of nucleosomes is inferred from the appearance of nucleosome-sized bubbles in the micrograph (Supplementary Fig.…”