Chromatin higher-order structures and gene regulation

Abstract

Genomic DNA in the eukaryotic nucleus is hierarchically packaged by histones into chromatin to fit inside the nucleus. The dynamics of higher-order chromatin compaction play a crucial role in transcription and other biological processes inherent to DNA. Many factors, including histone variants, histone modifications, DNA methylation, and the binding of non-histone architectural proteins regulate the structure of chromatin. Although the structure of nucleosomes, the fundamental repeating unit of chromatin, is clear, there is still much discussion on the higher-order levels of chromatin structure. In this review, we focus on the recent progress in elucidating the structure of the 30-nm chromatin fiber. We also discuss the structural plasticity/dynamics and epigenetic inheritance of higher-order chromatin and the roles of chromatin higher-order organization in eukaryotic gene regulation.

Figure 1. Models of the 30 nm Chromatin Fiber

Two well-known structural models for 30-nm chromatin fibers are proposed: one-start helix (solenoid) (a and c) and two-start helix (zig-zag) (b and d). At the top, a schematic representation is shown for the two different topologies of 30-nm chromatin fibers (a and b). The alternative nucleosomes are numbered from N1 to N8. In the solenoid model proposed by Rhodes and colleagues, the 30-nm chromatin fiber is an interdigitated one-start helix in which a nucleosome in the fiber interacts with its fifth and sixth neighbor nucleosomes [19]. Alternative helical gyres are colored blue and magenta (c). In the zigzag model suggested by Richmond and colleagues, the chromatin fiber is a two-start helix in which nucleosomes are arranged in a zig-zag manner such that a nucleoosme in the fiber binds to the second neighbor nucleosome[18,20]. Alternative nucleosomes pairs are colored blue and orange. Image courtesy of D. Rhodes.

Figure 2. Hierarchical folding and Plasticity of higher-order chromatin structures

A general scheme represent the folding of chromatin from 11-nm nucleosomal arrays (beads-on-string) to higher order chromatin structures including 30-nm chromatin fiber, fiber-fiber association, chromatin looping and positioning. Factors proposed to affect changes between different chromatin structures are shown.

Figure 3. Chromatin compaction mediated by architectural proteins

Electron microscopy images of the different types of chromatin compaction mediated by various chromatin architectural proteins discussed in the text. Untreated 12-mer and 25-mer reconstituted nucleosomal arrays was shown in the center (left, 25-mer arrays [G Li and D Reinberg, unpublished]; right, 12-mer arrays reproduced with permission from [88]). From a to f, 12-mer nucleosomal arrays bound with PRC1 (reproduced with permission from [86]), Sir3p (reproduced with permission from [92]), PRC2-Ezh1 (reproduced with permission from [87•]), MENT (reproduced with permission from [88]), MeCP2 (reproduced with permission from [89]), and L3MBTL1 (reproduced with permission from [81•]); g, Hypo-acetylated 25-mer nucleosomal arrays bound with H1 (G Li and D Reinberg, unpublished), all at approximately the same magnification.