Chromatin higher-order structure and dynamics

Abstract

The primary role of the nucleus as an information storage, retrieval, and replication site requires the physical organization and compaction of meters of DNA. Although it has been clear for many years that nucleosomes constitute the first level of chromatin compaction, this contributes a relatively small fraction of the condensation needed to fit the typical genome into an interphase nucleus or set of metaphase chromosomes, indicating that there are additional "higher order" levels of chromatin condensation. Identifying these levels, their interrelationships, and the principles that govern their occurrence has been a challenging and much discussed problem. In this article, we focus on recent experimental advances and the emerging evidence indicating that structural plasticity and chromatin dynamics play dominant roles in genome organization. We also discuss novel approaches likely to yield important insights in the near future, and suggest research areas that merit further study.

Figure 1.

The DNA path of a tetranucleosome as determined by X-ray diffraction. The structure consists of two stacks of nucleosomes, with linker DNA passing back and forth between them. Thus, the primary interactions occur between alternate rather than adjacent nucleosomes along the DNA strand, creating a zigzag architecture. From Schlach et al. 2005.

Figure 2.

EMANIC analysis of internucleosomal interactions. (A) Scheme of the EMANIC procedure. The two models for the structure of the chromatin 30-nm fiber, namely solenoid (Upper) and zigzag (Lower), lead to dominant i ± 1 and i ± 2 internucleosome interactions, respectively. (B–D) EM of nucleosome reconstitutes crosslinked in low salt without linker histone show few crosslinks. (E-I) With H1 present, ±2 interactions predominate. D′ and I′ diagram the nucleosome arrays corresponding to the adjacent EM images. From Grigoryev et al. 2009.

Figure 3.

Stereo pair of a section of nucleus in which a large region of chromosome is decorated with gold particles. Clear fiber-like structures of the order of 100 nm are seen. Scale is 500 nm. From Kireeva et al., 2008.

Figure 4.

(A) A large locus consisting of ∼4-Mbp region containing regions of gene “deserts” (red fluorescence) and gene clusters (green fluorescence) is seen in the nucleus in multiple configurations (C). In general, gene deserts are more closely associated with the heterochromatin at the nuclear periphery (B). Scale is 1 µm. From Shopland et al. 2006.

Figure 5.

Time sequence showing the extension of a metaphase chromosome in which the two ends are anchored by micropipettes. The diameter remains quite constant throughout. From Marko 2008.

Figure 6.

Extensible net model of mitotic chromosome structure derived from force-extension measurements. From Poirier and Marko 2002.

Figure 7.

Model of chromosome formation that incorporates the concept of a central axis enriched in condensins (red dots) and irregularly folded chromatin fibers. From Kireeva et al. 2004.

Figure 8.

The different forms of large-scale motion that contribute to chromatin dynamics. From Soutoglou and Misteli 2007.