Abstract
During the last few years, there has been a rapid increase in our knowledge of how chromatin is organized inside the nucleus. Techniques such as FISH (fluorescence in situ hybridization) have proved that chromosomes organize themselves in so-called CTs (chromosome territories). In addition, newly developed 3C (chromatin conformation capture) techniques have revealed that certain chromosomal regions tend to interact with adjacent regions on either the same chromosome or adjacent chromosomes, and also that regions in close proximity are replicated simultaneously. Furthermore, transcriptionally repressed or active areas occupy different nuclear compartments. Another new technique, named DamID (DNA adenine methyltransferase identification), has strengthened the notion that transcriptionally repressed genes are often found in close association with the nuclear membrane, whereas transcriptionally active regions are found in the more central regions of the nucleus. However, in response to various stimuli, transcriptionally repressed regions are known to relocalize from the nuclear lamina to the interior of the nucleus, leading to a concomitant up-regulation of otherwise silenced genes. Taken together, these insights are of great interest for the relationship between chromosomal spatial organization and genome function. In the present article, we review recent advances in this field with a focus on mammalian cells and the eukaryotic model organism Schizosaccharomyces pombe.
Highlights
Methods for studying nuclear organizationBefore the advent of high-throughput molecular biology methods, microscopy was the main method to study the arrangement of chromosomes within the cell nucleus
We have touched upon different aspects of how the nuclear organization of chromatin is associated with transcription and replication, with a focus on studies conducted in fission yeast and humans
Studies in these two evolutionarily distant organisms show that the distribution of chromatin and chromosomes are non-random
Summary
Before the advent of high-throughput molecular biology methods, microscopy was the main method to study the arrangement of chromosomes within the cell nucleus Molecular biology methods such as ChIP (chromatin immunoprecipitation) are the main approach of studying the interaction between proteins and specific genomic sites. For live-cell imaging purposes, generating a fusion between the protein of interest and a fluorescent tag is an important approach to study chromatin organization. FISH (fluorescence in situ hybridization) is based on fluorescently labelled oligonucleotide probes that bind complementarily to either DNA or RNA. This method cannot be used for live-cell imaging purposes, since cells must be fixed before hybridization with the probe. All 24 human chromosomes could be labelled in
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