Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions

• Published in: Nature reviews. Genetics Vol. 8; no. 2; pp. 104 - 115
• Main Authors: Lanctôt, Christian, Cheutin, Thierry, Cremer, Marion, Cavalli, Giacomo, Cremer, Thomas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2007; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biological Transport - physiology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Nucleus - genetics; Cell Nucleus - physiology; Chromatin; Chromatin - genetics; Chromatin - metabolism; Chromatin - physiology; Chromosomes; Drosophila; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Gene Function; Gene loci; Genetic aspects; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome - genetics; Genomes; Human Genetics; Life Sciences; Microarray Analysis - methods; Models, Genetic; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Physiological aspects; review-article; Time Factors; Topography; Transcriptional Activation; Gene expression; Genome; Regulation(control)
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg2041

Key Points Chromatin is mobile in the cell nucleus and undergoes movements that are best described as constrained diffusion. The extent of chromatin mobility is maximal in the early G1 phase of the cell cycle and can change depending on the differentiation status of the cell. Chromatin mobility is limited by structural constraints, as reflected in the territorial organization of chromosomes, the gene-density-related polarity of chromosome territories and the clustering of active and inactive chromatin in the nucleus. Chromatin movements away from the nuclear periphery or constitutive heterochromatin have been associated with gene activity in certain mammalian cell types. As a result of chromatin mobility, genomic regions interact with each other in the nucleus, a phenomenon that is referred to as 'gene kissing'. Recently, cases in which gene kissing has an important role in transcriptional regulation have been reported. Recent technological advances have allowed the large-scale identification of interacting loci. Initial results indicate that gene–gene interactions are driven in large part by the surrounding chromatin features (for example, transcriptional activity, histone code and gene content), rather than by a specific gene function being shared by the interacting partners. A dynamic view of nuclear function is emerging, in which genomic regions undergo repositioning relative to each other and to nuclear subcompartments. Increasing evidence points to an important contribution of these movements in the regulation of gene expression. The regulation of gene expression is mediated by interactions between chromatin and protein complexes. The importance of where and when these interactions take place in the nucleus is currently a subject of intense investigation. Increasing evidence indicates that gene activation or silencing is often associated with repositioning of the locus relative to nuclear compartments and other genomic loci. At the same time, however, structural constraints impose limits on chromatin mobility. Understanding how the dynamic nature of the positioning of genetic material in the nuclear space and the higher-order architecture of the nucleus are integrated is therefore essential to our overall understanding of gene regulation.