There are an increasing number of studies reporting the movement of gene loci and whole chromosomes to new compartments within interphase nuclei. Some of the movements can be rapid, with relocation of parts of the genome within less than 15 min over a number of microns. Some of these studies have also revealed that the activity of motor proteins such as actin and myosin are responsible for these long-range movements of chromatin. Within the nuclear biology field, there remains some controversy over the presence of an active nuclear acto–myosin motor in interphase nuclei. However, both actin and myosin isoforms are localized to the nucleus, and there is a requirement for rapid and directed movements of genes and whole chromosomes and evidence for the involvement of motor proteins in this relocation. The presence of nuclear motors for chromatin movement is thus an important and timely debate to have.

Since the advent of FISH (fluorescence in situ hybridization), there have been major advances in our understanding of how the genome is organized in interphase nuclei. Indeed, this organization is found to be non-random and individual chromosomes occupy discrete regions known as territories. Determining the factors that drive the spatial positioning of these territories within nuclei has caused much debate; however, in proliferating cells, there is evidently a correlation between radial positioning and gene density. Indeed, gene-poor chromosomes tend to be located towards the nuclear edge, while those that are more gene-rich are positioned more internally. These observations pose a number of questions: first, what is the function of this global organization and, secondly, is it representative of that occurring at a more local scale? During the course of this review, these questions will be considered, in light of the current literature regarding the role of transcription factories and the nuclear matrix in interphase genome organization.

HGPS (Hutchinson–Gilford progeria syndrome) is a rare genetic disease affecting children causing them to age and die prematurely. The disease is typically due to a point mutation in the coding sequence for the nuclear intermediate-type filament protein lamin A and gives rise to a dominant-negative splice variant named progerin. Accumulation of progerin within nuclei causes disruption to nuclear structure, causes and premature replicative senescence and increases apoptosis. Now it appears that accumulation of progerin may have more widespread effects than previously thought since the demonstration that the presence and distribution of some nucleolar proteins are also adversely affected in progeria cells. One of the major breakthroughs both in the lamin field and for this syndrome is that many of the cellular defects observed in HGPS patient cells and model systems can be restored after treatment with a class of compounds known as FTIs (farnesyltransferase inhibitors). Indeed, it is demonstrated that FTI-277 is able to completely restore nucleolar antigen localization in treated progeria cells. This is encouraging news for the HGPS patients who are currently undergoing clinical trials with FTI treatment.

The laminopathy Hutchinson–Gilford progeria syndrome (HGPS) is caused by the mutant lamin A protein progerin and leads to premature aging of affected children. Despite numerous cell biological and biochemical insights into the basis for the cellular abnormalities seen in HGPS, the mechanism linking progerin to the organismal phenotype is not fully understood. To begin to address the mechanism behind HGPS using Drosophila melanogaster , we have ectopically expressed progerin and lamin A. We found that ectopic progerin and lamin A phenocopy several effects of laminopathies in developing and adult Drosophila , but that progerin causes a stronger phenotype than wild-type lamin A.

The nuclear matrix has remained a contentious structure for decades; many believe that it is an artefact of harsh non-physiological procedures. However, its visualization using milder experimental techniques is leading to its general acceptance by the scientific community. It is a permanent network of core filaments underlying thicker fibres which is proposed to be a platform for numerous important nuclear activities such as transcription and DNA repair. Interestingly, A- and B-type lamin proteins and emerin are components of this nuclear structure; however, they are often referred to only as nuclear envelope proteins. The present mini-review intends to provide an overview of the nuclear matrix, mentioning both its constituents and functional significance. The impact of disease-causing mutations in both emerin and lamin proteins on the structure's ability to regulate and mediate nuclear processes is then discussed.

Rapid interphase chromosome territory repositioning appears to function through the action of nuclear myosin and actin, in a nuclear motor complex. We have found that chromosome repositioning when cells leave the cell cycle is not apparent in cells that have mutant lamin A or that are lacking emerin. We discuss the possibility that there is a functional intranuclear complex comprising four proteins: nuclear actin, lamin A, emerin and nuclear myosin. If any of the components are lacking or aberrant, then the nuclear motor complex involved in moving chromosomes or genes will be dysfunctional, leading to an inability to move chromosomes in response to signalling events.