Chromatin without the 30-nm fiber: constrained disorder instead of hierarchical folding

Abstract

Several hierarchical levels of DNA packaging are believed to exist in chromatin, starting from a 10-nm chromatin fiber that is further packed into a 30-nm fiber. Transitions between the 30-nm and 10-nm fibers are thought to be essential for the control of chromatin transcriptional status. However, recent studies demonstrate that in the nuclei, DNA is packed in tightly associated 10-nm fibers that are not compacted into 30-nm fibers. Additionally, the accessibility of DNA in chromatin depends on the local mobility of nucleosomes rather than on decompaction of chromosome regions. These findings argue for reconsidering the hierarchical model of chromatin packaging and some of the basic definitions of chromatin. In particular, chromatin domains should be considered as three-dimensional objects, which may include genomic regions that do not necessarily constitute a continuous domain on the DNA chain.

Keywords: 3D genome organization; DNA packaging; chromatin domain; chromatin fiber; histone modifications; nucleosome mobility.

Figure 1. Schematic illustrating a possible pathway for the condensation of several 10-nm fibers into a compact heterochromatin-like structure. See description in the text.

Figure 2. Mechanisms of signal spreading in chromatin (exemplified by the spreading of histone acetylation). (A) A classical view of the linear spreading of a signal in two directions along the chromatin fiber. (B) Three-dimensional spreading of a signal in all directions from a nucleation center resulting in modification of multiple chromatin regions both in cis and in trans.