Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

Background

Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified.

Results

To search for such proteins, 23 nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells.

Conclusions

The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.     

An ensemble of B-DNA dinucleotide geometries lead to characteristic nucleosomal DNA structure and provide plasticity required for gene expression

Background  

A nucleosome is the fundamental repeating unit of the eukaryotic chromosome. It has been shown that the positioning of a majority of nucleosomes is primarily controlled by factors other than the intrinsic preference of the DNA sequence. One of the key questions in this context is the role, if any, that can be played by the variability of nucleosomal DNA structure.     

Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Background  

Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.     

Immunostaining of modified histones defines high-level features of the human metaphase epigenome

Background  

Immunolabeling of metaphase chromosome spreads can map components of the human epigenome at the single cell level. Previously, there has been no systematic attempt to explore the potential of this approach for epigenomic mapping and thereby to complement approaches based on chromatin immunoprecipitation (ChIP) and sequencing technologies.     

High cell density and latent membrane protein 1 expression induce cleavage of the mixed lineage leukemia gene at 11q23 in nasopharyngeal carcinoma cell line

Background  

Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes.     

Dynamic expression of Dab2 in the mouse embryonic central nervous system

Background  

Dab2, one of two mammalian orthologs of Drosophila Disabled, has been shown to be involved in cell positioning and formation of visceral endoderm during mouse embryogenesis, but its role in neuronal development is not yet fully understood. In this report, we have examined the localization of the Dab2 protein in the mouse embryonic central nervous system (CNS) at different developmental stages.     

Serious limitations of the QTL/Microarray approach for QTL gene discovery

Background  

It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed.     

Decreased Rate of Evolution in Y Chromosome STR Loci of Increased Size of the Repeat Unit

Background

Polymorphic Y chromosome short tandem repeats (STRs) have been widely used in population genetic and evolutionary studies. Compared to di-, tri-, and tetranucleotide repeats, STRs with longer repeat units occur more rarely and are far less commonly used.

Principal Findings

In order to study the evolutionary dynamics of STRs according to repeat unit size, we analysed variation at 24 Y chromosome repeat loci: 1 tri-, 14 tetra-, 7 penta-, and 2 hexanucleotide loci. According to our results, penta- and hexanucleotide repeats have approximately two times lower repeat variance and diversity than tri- and tetranucleotide repeats, indicating that their mutation rate is about half of that of tri- and tetranucleotide repeats. Thus, STR markers with longer repeat units are more robust in distinguishing Y chromosome haplogroups and, in some cases, phylogenetic splits within established haplogroups.

Conclusions

Our findings suggest that Y chromosome STRs of increased repeat unit size have a lower rate of evolution, which has significant relevance in population genetic and evolutionary studies.     

Exploitation of the interaction of measles virus fusogenic envelope proteins with the surface receptor CD46 on human cells for microcell-mediated chromosome transfer

Background  

Microcell-mediated chromosome transfer (MMCT) is a technique by which a chromosome(s) is moved from donor to recipient cells by microcell fusion. Polyethylene glycol (PEG) has conventionally been used as a fusogen, and has been very successful in various genetic studies. However, PEG is not applicable for all types of recipient cells, because of its cell type-dependent toxicity. The cytotoxicity of PEG limits the yield of microcell hybrids to low level (10^-6 to 10^-5 per recipient cells). To harness the full potential of MMCT, a less toxic and more efficient fusion protocol that can be easily manipulated needs to be developed.     

Amplification of multiple genomic loci from single cells isolated by laser micro-dissection of tissues

Background  

Whole genome amplification (WGA) and laser assisted micro-dissection represent two recently developed technologies that can greatly advance biological and medical research. WGA allows the analysis of multiple genomic loci from a single genome and has been performed on single cells from cell suspensions and from enzymatically-digested tissues. Laser micro-dissection makes it possible to isolate specific single cells from heterogeneous tissues.     

The architecture of chicken chromosome territories changes during differentiation

Background  

Between cell divisions the chromatin fiber of each chromosome is restricted to a subvolume of the interphase cell nucleus called chromosome territory. The internal organization of these chromosome territories is still largely unknown.     

Supracubital perineurioma misdiagnosed as carpal tunnel syndrome: case report

Background  

Perineuriomas have been defined as tumorous lesions of the peripheral nerves which derive from perineurial cell proliferation and may be associated with abnormalities on chromosome 22.     

<Emphasis Type="Italic">Bacillus subtilis</Emphasis> actin-like protein MreB influences the positioning of the replication machinery and requires membrane proteins MreC/D and other actin-like proteins for proper localization

Background  

Bacterial actin-like proteins have been shown to perform essential functions in several aspects of cellular physiology. They affect cell growth, cell shape, chromosome segregation and polar localization of proteins, and localize as helical filaments underneath the cell membrane. Bacillus subtilis MreB and Mbl have been shown to perform dynamic motor like movements within cells, extending along helical tracks in a time scale of few seconds.     

Altered chromosomal positioning, compaction, and gene expression with a lamin A/C gene mutation

Background

Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression.

Methods/Findings

To investigate the hypothesis that mutant lamin A/C changes the lamina''s ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction.

Conclusions

These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered.     

A plant MinD homologue rescues Escherichia coli HL1 mutant (ΔMinDE) in the absence of MinE

Background  

In E. coli, the Min operon (MinCDE) plays a key role in determining the site of cell division. MinE oscillates from the middle to one pole or another to drive the MinCD complex to the end of the cell. The MinCD complex prevents FtsZ ring formation and the subsequent cell division at cell ends. In Arabidopsis thaliana, a homologue of MinD has been shown to be involved in the positioning of chloroplast division site.     

Chromosomal duplications and cointegrates generated by the bacteriophage lamdba Red system in Escherichia coli K-12

Background  

An Escherichia coli strain in which RecBCD has been genetically replaced by the bacteriophage λ Red system engages in efficient recombination between its chromosome and linear double-stranded DNA species sharing sequences with the chromosome. Previous studies of this experimental system have focused on a gene replacement-type event, in which a 3.5 kbp dsDNA consisting of the cat gene and flanking lac operon sequences recombines with the E. coli chromosome to generate a chloramphenicol-resistant Lac- recombinant. The dsDNA was delivered into the cell as part of the chromosome of a non-replicating λ vector, from which it was released by the action of a restriction endonuclease in the infected cell. This study characterizes the genetic requirements and outcomes of a variety of additional Red-promoted homologous recombination events producing Lac+ recombinants.     

Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina

Background  

The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC) and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described.     

A new mixture model approach to analyzing allelic-loss data using Bayes factors

Background  

Allelic-loss studies record data on the loss of genetic material in tumor tissue relative to normal tissue at various loci along the genome. As the deletion of a tumor suppressor gene can lead to tumor development, one objective of these studies is to determine which, if any, chromosome arms harbor tumor suppressor genes.     

The XMAP215-family protein DdCP224 is required for cortical interactions of microtubules

Background  

Interactions of peripheral microtubule tips with the cell cortex are of crucial importance for nuclear migration, spindle orientation, centrosome positioning and directional cell movement. Microtubule plus end binding proteins are thought to mediate interactions of microtubule tips with cortical actin and membrane proteins in a dynein-dependent manner. XMAP215-family proteins are main regulators of microtubule plus end dynamics but so far they have not been implicated in the interactions of microtubule tips with the cell cortex.