Nucleosome distribution and linker DNA: connecting nuclear function to dynamic chromatin structure

Abstract

Genetic information in eukaryotes is managed by strategic hierarchical organization of chromatin structure. Primary chromatin structure describes an unfolded nucleosomal array, often referred to as "beads on a string". Chromatin is compacted by the nonlinear rearrangement of nucleosomes to form stable secondary chromatin structures. Chromatin conformational transitions between primary and secondary structures are mediated by both nucleosome-stacking interactions and the intervening linker DNA. Chromatin model system studies find that the topography of secondary structures is sensitive to the spacing of nucleosomes within an array. Understanding the relationship between nucleosome spacing and higher order chromatin structure will likely yield important insights into the dynamic nature of secondary chromatin structure as it occurs in vivo. Genome-wide nucleosome mapping studies find the distance between nucleosomes varies, and regions of uniformly spaced nucleosomes are often interrupted by regions of nonuniform spacing. This type of organization is found at a subset of actively transcribed genes in which a nucleosome-depleted region near the transcription start site is directly adjacent to uniformly spaced nucleosomes in the coding region. Here, we evaluate secondary chromatin structure and discuss the structural and functional implications of variable nucleosome distributions in different organisms and at gene regulatory junctions.

Fig. 1

Schematic representation of three different models for secondary chromatin structure and linker histone. (a) Two-start helical ribbon. (b) Two-start crossed-linker. (c) One-start solenoid fiber. Fiber long axes (top), cross sectional views (middle) and basic nucleosome arrangements (bottom) are shown for each model.

Fig. 2

Fiber geometry as a function of nucleosome repeat length (NRL). Average fiber diameter (left) and nucleosome packing density (right) obtained from compacted nucleosomal arrays using EM or X-ray scattering techniques are plotted against their respective NRL. Approximation of NRLs from various eukaryotes and cell-types obtained from endogenous chromatin samples (van Holde, 1989) are indicated by dashed lines.

Fig. 3

Schematic representation of dynamic secondary chromatin structure at gene regulatory junctions. Repressive chromatin structure establishes the inactive state. Gene activation by various nuclear signal transduction pathways target the -1 nucleosome region. Gene secondary chromatin structure transitions to a bipartite ‘open-gate’ conformation consisting of a disrupted -1 nucleosomal region in the gene promoter followed by a ‘specialized’ secondary chromatin structure in the coding region. The ‘open-gate’ conformation allows RNAPII access to the TSS for transcription initiation. The ‘specialized’ secondary chromatin structure facilitates transcription via unknown mechanisms. RNAPII-dependent processes actively re-establish nucleosome phasing in the coding region and maintain the ‘open-gate’ secondary chromatin structure for multiple rounds of mRNA synthesis.