Chromatin: Physical Organization

Abstract

In most eukaryotic cells, DNA is not free, but complexed with proteins to form chromatin. The fundamental unit of chromatin physical organization is the nucleosome, in which 146bp of DNA is wrapped on an octameric core of small, highly basic proteins, the histones. How this beads-on-a-string primary structure of chromatin is folded and compacted in the living nucleus continues to be a challenging topic of research. The primary organization is modulated in many ways, including distance between nucleosomes, postsynthetic modification of histones, the presence of variant histones, and the presence of nonhistone chromosomal proteins. Although the ubiquitous presence of nucleosome is undisputed, and its compaction into chromatin fibers well established through in vitro studies, neither nucleosomes nor fibers are typically seen in whole nuclei or sections of nuclei. This is likely due to the remarkably high level of chromatin compaction in vivo, coupled with a tendency of close-packed arrays of nucleosomes to assume a molten-globule state. Recently, dramatic progress in understanding in vivo long-range genomic interactions has been achieved by chromatin conformation capture, a family of techniques using chemical cross-linking to capture neighboring segments of chromatin in three-dimensional space. The nucleus is highly dynamic, with many of its associated proteins showing high levels of intranuclear mobility.