- Chromatin is wonderful stuff.
- Seminars in Cell & Developmental Biology
- Volume | Issue number
- 18 | 5
- Pages (from-to)
- Document type
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
Chromatin molecules have properties that set them aside from all other biomacromolecules in the cell. (i) Chromosomes, which are single chromatin molecules, are the largest macromolecules in eukaryotic cells. (ii) Chromatin molecules carry the cell's genetic and epigenetic information and all control elements that regulate and, importantly, orchestrate expression of tenths of thousands of genes. (iii) Chromatin fibers are extremely highly folded inside the cell nucleus. Moreover, chromatin folding varies considerably from cell to cell, even in otherwise identical cells. Despite this, chromatin can be accurately duplicated and faithfully separated over the two daughter cells during cell division. (iv) The highly folded chromatin fiber acts as a scaffold that spatially organizes processes inside the nucleus, such as transcription and replication. This chromatin-based compartmentalization of the nucleus is a key element in the regulation of genome function. (v) Chromatin-associated processes often are single molecule processes in which proteins that freely diffuse inside the nucleus have to find and assemble on unique sequence elements, e.g. a specific promoter, of the chromatin fiber. (vi) The structure of chromatin shows remarkable plasticity. Depending on regulatory signals its chemical structure changes continuously (e.g. due to histone modifications), its protein composition alters (e.g. incorporation of variant histones and the assembly and disassembly of transcription complexes) and folding inside the nucleus may change dramatically (e.g. depending on epigenetic changes and changes in transcriptional activity). These properties all contribute to and probably are essential for proper functioning of the eukaryotic genome.
Research aiming to understand chromatin properties and unravel underlying physical principles and molecular mechanisms is hampered by the fact that we have no tools to directly visualize and analyze the chromatin fiber inside the cell. Also, chromatin structure in part depends on weak interactions that are lost upon opening the cell, making biochemical approaches difficult. To unravel chromatin-related enigmas we have to rely on combining a broad range of strategies and techniques.
This special issue addresses a number of important aspects of chromatin research that are not yet encountered often in the main stream scientific literature. In the first paper Van Holde and Zlatanova  discuss our present understanding of what probably is a basic folding state of chromatin, the 30 nm fiber. One way to unravel principles of chromatin folding is the development of predictive computational models, which define precise questions that can be addressed experimentally. Langowski and Heermann  present a sample of this by modeling the nucleosomal fiber and analyzing its properties, such as flexibility as a function of linker histone H1 binding. Hancock  discusses an often overlooked aspect of biological organization in general and chromatin structure in particular: macromolecular crowding. It is made highly plausible that crowding phenomena are a key element in defining chromatin structure in vivo. The paper of Fakan and Van Driel  discusses an intriguing aspect of spatial organization of our genome. Transcription and replication occur exclusively at the surface of compact subchromosomal chromatin domains, which poses major constrains to the way the chromatin fiber is folded inside the interphase nucleus. Dorman et al.  E.R. Dorman, A.M. Bushey and V.G. Corces, The role of insulator elements in large-scale chromatin structure in interphase, Sem Cell Dev Biol 18 (2007), pp. 682-690. Article | PDF (1131 K) | View Record in Scopus | Cited By in Scopus (17) summarize our understanding of the role of insulator elements in the genome in the spatial organization of the chromatin fiber. Insulator sequences may constitute a major class of chromatin-chromatin interactions. Sexton et al.  describe another important type of interchromatin interactions: transcription factories. In this type of structures transcriptionally active genes from different part of the chromatin fiber and from different chromosomes come together in the interphase nucleus, imposing further constrains on the large-scale folding pattern. Chuang and Belmont  address the issue of directed movement of parts of the chromatin fiber in relation to compartmentalization of the interphase nucleus. Finally, Goetze et al.  discuss various aspects of the large-scale organization of the chromatin fiber in mammalian cells.
Together, these papers give a good overview of the different ways structure-function relationships of the chromatin fiber are addressed and summarize the main questions that we have to deal with in the forthcoming years.
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