On the role of inter-nucleosomal interactions and intrinsic nucleosome dynamics in chromatin function

Abstract

Evidence is emerging that many diseases result from defects in gene functions, which, in turn, depend on the local chromatin environment of a gene. However, it still remains not fully clear how chromatin activity code is 'translated' to the particular 'activating' or 'repressing' chromatin structural transition. Commonly, chromatin remodeling in vitro was studied using mononucleosomes as a model. However, recent data suggest that structural reorganization of a single mononucleosome is not equal to remodeling of a nucleosome particle under multinucleosomal content - such as, interaction of nucleosomes via flexible histone termini could significantly alter the mode (and the resulting products) of nucleosome structural transitions. It is becoming evident that a nucleosome array does not constitute just a 'polymer' of individual 'canonical' nucleosomes due to multiple inter-nucleosomal interactions which affect nucleosome dynamics and structure. It could be hypothesized, that inter-nucleosomal interactions could act in cooperation with nucleosome inherent dynamics to orchestrate DNA-based processes and promote formation and stabilization of highly-dynamic, accessible structure of a nucleosome array. In the proposed paper we would like to discuss the nucleosome dynamics within the chromatin fiber mainly as it pertains to the roles of the structural changes mediated by inter-nucleosomal interactions.

Keywords: Chromatin; Chromatin remodeling; Gene activity; Histones; Nucleosomes; Transcription.

Graphical abstract

Fig. 1

A schematic illustration of a possible structure suggested for the altosome .

Fig. 2

A schematic illustration of different abilities of ISW1a and ISW1b to remodel dinucleosomes on the example of chromatinized DNA templates 24N4N31 and 24N42N31 (the numbers show the length (bp) of spacer DNA flanking the 601 nucleosome positioning sequences “N”). Positioned nucleosomes are depicted as gray ovals. Depending on the initial nucleosome spacing, ISW1a positions histone octamers closer or further from each other. In contrast, ISW1b randomly distributes histone octamers on the DNA (unpositioned nucleosomes are shown in light gray color).

Fig. 3

A sketch illustrating DNase I susceptibility of internucleosomal DNA in dinucleosomes remodeled with ISW2. Nucleosomes were assembled on 3′ end-radiolabeled DNA templates 24N10N31, 24N28N31 and 24N10N31 (in which the numbers show the length (bp) of spacer DNA flanking the 601 nucleosome positioning sequences “N”). The gray ovals schematically depict nucleosomes. The insert on each drawing shows a segment of the dinucleosome DNase I footprint ladder (gel direction is from left to right). (A-C) depict unremodeled 24N10N31, 24N28N31 and 24N42N31 dinucleosomes, (D and E) show unremodeled and Isw2-remodeled 24N10N31, respectively. The filled circles indicate the DNase I cleavage sites observed in both unremodeled and remodeled templates, the asterisks indicate extra DNase I sites in remodeled templates. The schemes are shown for illustration purposes and do not maintain exact proportions (for more information see ([98]).

Fig. 4

A sketch of a possible structure suggested for a compact nucleosome dimer .

Fig. 5

A schematic illustration of nucleosome gaping transition – an about 30° ‘opening’ of the nucleosome in the direction normal to the DNA plane. The complex alterations of the histone core octamer (which include distortions of the histone dimer-tetramer interactions) are not depicted.

Fig. 6

Possible role of internucleosomal interactions and inherent nucleosome dynamics in RNA polymerase II transcription through arrayed nucleosomes. (A) Internucleosomal interactions facilitate transient uncoiling of DNA that allows RNA- pol II to enter the nucleosome. (B) RNA Pol II enters the nucleosomes and pauses at the region of strong histone-DNA interactions. (C) recoiling of DNA behind the polymerase promotes formation of temporary DNA Ǿ-loop, that is required to position RNA pol II on the DNA, and also (D) orchestrates uncoiling the promoter-distal portion of the nucleosome that allows RNA pol II to “read” through the rest of the nucleosome. (E) Neighboring nucleosomes could transiently accommodate the ‘transcribed’ histone octamer (or its’ dissociated components) and thus, promote further reinstatement of its position on the DNA.