Chromatin organization in relation to the nuclear periphery

Abstract

In the limited space of the nucleus, chromatin is organized in a dynamic and non-random manner. Three ways of chromatin organization are compaction, formation of loops and localization within the nucleus. To study chromatin localization it is most convenient to use the nuclear envelope as a fixed viewpoint. Peripheral chromatin has both been described as silent chromatin, interacting with the nuclear lamina, and active chromatin, interacting with nuclear pore proteins. Current data indicate that the nuclear envelope is a reader as well as a writer of chromatin state, and that its influence is not limited to the nuclear periphery. Ó 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.Keywords: Chromatin; Nuclear lamina; Lamin; Nuclear pore complex; Nucleoporin; Nup Chromatin organization by compactionTo fit into the limited space of the nucleus and still carry out its function, human genomic DNA is extensively folded, making it about 10 000-fold more compact. Several levels of compaction have been described: the nucleosome, the 30 nm fiber and higher order chromatin structure.The lowest level of chromatin compaction is the nucleosome. A 5-10-fold compaction is achieved when 146-165 base pairs of DNA are wound around an octamer of histone proteins, which is referred to as the nucleosome core particle. Besides providing a structural basis for the first compaction level, histones can also affect chromatin organization by being chemically modified at their tail or by being replaced by variants of the core histones. These modifications have a major impact on chromatin structure and gene expression by influencing the binding of proteins to the nucleosome, the affinity of DNA for the histone octamer and the stability of higher order structures [1]. Thus, at this low level of organization the nucleosome offers a powerful mechanism for controlling chromatin structure in a local, non-random manner.Findings on the second level of compaction are more ambiguous. In vitro, oligonucleosomes are able to organize themselves into a compact fiber with a diameter of 30 nm in absence of nuclear proteins but in the presence of divalent cations. In vivo, estimated nuclear cation concentrations are even higher than the concentration used in experiments, aiding the compaction [2]. This compaction could be further modulated by the involvement of numerous nuclear proteins in vivo. For example, histone tails and histone H1 further stabilize this structure by binding to linker DNA.All condensation levels above the 30 nm fiber are indicated as higher order chromatin structure. This poorly defined structure may consist of several levels of condensation and is very dynamic and thus hard to study. The question has even been raised whether there is a uniform higher order structure at all, or whether chromatin is too dynamic to form stable structures at a higher order level [3].All levels of compaction are not equal throughout the cell, leading to more accessible and less accessible regions. D...

An epichromatin epitope: Persistence in the cell cycle and conservation in evolution

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“…Describing these principles is a major goal of cell biology and encompasses understanding the interphase nucleus, the mitotic chromosome and other chromatin structural states. [1][2][3][4][5] A major advance in our understanding of the organization of chromatin came with the description of chromosome territories (CTs), 6,7 which demonstrated that the individuality of mitotic chromosomes is preserved, albeit in a swollen form, within the interphase nucleus. Evidence has also been presented that within these territories chromatin exists in "knot-free" globules, analogous to the nucleosomal "beads-on-a-string"; but at…”

Nuclear lamins: key regulators of nuclear structure and activities

“…In addition, gene-poor chromosomes are peripherally located, whereas gene-rich chromosomes are more centrally located [96,97] [103].…”

Dynamics of the Plant Nuclear Envelope and Nuclear Pore

“…Inserted at these sites are the nuclear pore complexes (NPCs), large protein conglomerates responsible for the selective nuclear import and export of macromolecules (D'Angelo and . Chromatin association with the nuclear pores and the NE is involved in gene activation and repression, respectively (Akhtar and Gasser, 2007;Kalverda et al, 2008;Capelson and Hetzer, 2009). In higher organisms, the NE plays a role in the dissociation and reformation of the nucleus during cell division (Kutay and Hetzer, 2008).…”