Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations.

ABSTRACT: After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.

SUBMITTER: Branco MR

PROVIDER: S-EPMC1440941 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Transcription-dependent radial distribution of TCF7L2 regulated genes in chromosome territories.

Project description:Human chromosomes occupy distinct territories in the interphase nucleus. Such chromosome territories (CTs) are positioned according to gene density. Gene-rich CTs are generally located in the center of the nucleus, while gene-poor CTs are positioned more towards the nuclear periphery. However, the association between gene expression levels and the radial positioning of genes within the CT is still under debate. In the present study, we performed three-dimensional fluorescence in situ hybridization experiments in the colorectal cancer cell lines DLD-1 and LoVo using whole chromosome painting probes for chromosomes 8 and 11 and BAC clones targeting four genes with different expression levels assessed by gene expression arrays and RT-PCR. Our results confirmed that the two over-expressed genes, MYC on chromosome 8 and CCND1 on chromosome 11, are located significantly further away from the center of the CT compared to under-expressed genes on the same chromosomes, i.e., DLC1 and SCN3B. When CCND1 expression was reduced after silencing the major transcription factor of the WNT/β-catenin signaling pathway, TCF7L2, the gene was repositioned and mostly detected in the interior of the CT. Thus, we suggest a non-random distribution in which over-expressed genes are located more towards the periphery of the respective CTs.

| S-EPMC7906436 | biostudies-literature

Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription.

Project description:The 3D structure of the genome plays a key role in regulatory control of the cell. Experimental methods such as high-throughput chromosome conformation capture (Hi-C) have been developed to probe the 3D structure of the genome. However, it remains a challenge to deduce from these data chromosome regions that are colocalized and coregulated. Here, we present an integrative approach that leverages 1D functional genomic features (e.g., epigenetic marks) with 3D interactions from Hi-C data to identify functional interchromosomal interactions. We construct a weighted network with 250-kb genomic regions as nodes and Hi-C interactions as edges, where the edge weights are given by the correlation between 1D genomic features. Individual interacting clusters are determined using weighted correlation clustering on the network. We show that intermingling regions generally fall into either active or inactive clusters based on the enrichment for RNA polymerase II (RNAPII) and H3K9me3, respectively. We show that active clusters are hotspots for transcription factor binding sites. We also validate our predictions experimentally by 3D fluorescence in situ hybridization (FISH) experiments and show that active RNAPII is enriched in predicted active clusters. Our method provides a general quantitative framework that couples 1D genomic features with 3D interactions from Hi-C to probe the guiding principles that link the spatial organization of the genome with regulatory control.

| S-EPMC5748172 | biostudies-literature

Expansion of chromosome territories with chromatin decompaction in BAF53-depleted interphase cells.

Project description:Chromosomes are compartmentalized into discrete chromosome territories during interphase in mammalian cells. A chromosome territory is generated by the tendency of chromatin to occupy the smallest shell volume, which is determined by the polymeric properties and interactions of the internal meshwork of the chromatin fiber. Here, we show that BAF53 knockdown by small interfering RNA interference led to the expansion of chromosome territories. This was accompanied by a reduction in chromatin compaction, an increase in the micrococcal nuclease sensitivity of the chromatin, and an alteration in H3-K9 and H3-K79 dimethylation. Interestingly, the BAF53 knockdown cells suffer a cell cycle defect. Despite the significant irregularity and decompaction of the polynucleosomes isolated from the BAF53 knockdown cells, the chromatin loading of H1 and core histones remained unaltered, as did the nucleosome spacing. The histone hyperacetylation and down-regulation of BRG-1, mBrm, and Tip49, the catalytic components of the SWI/SNF complex and the TIP60 complex, respectively, did not expand chromosome territories. These results indicate that BAF53 contributes to the polymeric properties and/or the internal meshwork interactions of the chromatin fiber probably via a novel mechanism.

| S-EPMC1995741 | biostudies-literature

Quantitative detection of rare interphase chromosome breaks and translocations by high-throughput imaging.

Project description:We report a method for the sensitive detection of rare chromosome breaks and translocations in interphase cells. HiBA-FISH (High-throughput break-apart FISH) combines high-throughput imaging with the measurement of the spatial separation of FISH probes flanking target genome regions of interest. As proof-of-principle, we apply hiBA-FISH to detect with high sensitivity and specificity rare chromosome breaks and translocations in the anaplastic large cell lymphoma breakpoint regions of NPM1 and ALK. This method complements existing approaches to detect translocations by overcoming the need for precise knowledge of translocation breakpoints and it extends traditional FISH by its quantitative nature.

| S-EPMC4531802 | biostudies-literature

Mitotic chromosome binding predicts transcription factor properties in interphase.

Project description:Mammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/non-specific DNA binding. How these properties affect their ability to occupy specific genomic sites and modify the epigenetic landscape is unclear. The association of TFs with mitotic chromosomes observed by fluorescence microscopy is largely mediated by non-specific DNA interactions and differs broadly between TFs. Here we combine quantitative measurements of mitotic chromosome binding (MCB) of 501 TFs, TF mobility measurements by fluorescence recovery after photobleaching, single molecule imaging of DNA binding, and mapping of TF binding and chromatin accessibility. TFs associating to mitotic chromosomes are enriched in DNA-rich compartments in interphase and display slower mobility in interphase and mitosis. Remarkably, MCB correlates with relative TF on-rates and genome-wide specific site occupancy, but not with TF residence times. This suggests that non-specific DNA binding properties of TFs regulate their search efficiency and occupancy of specific genomic sites.

| S-EPMC6353955 | biostudies-literature

Condensin II promotes the formation of chromosome territories by inducing axial compaction of polyploid interphase chromosomes.

Project description:The eukaryotic nucleus is both spatially and functionally partitioned. This organization contributes to the maintenance, expression, and transmission of genetic information. Though our ability to probe the physical structure of the genome within the nucleus has improved substantially in recent years, relatively little is known about the factors that regulate its organization or the mechanisms through which specific organizational states are achieved. Here, we show that Drosophila melanogaster Condensin II induces axial compaction of interphase chromosomes, globally disrupts interchromosomal interactions, and promotes the dispersal of peri-centric heterochromatin. These Condensin II activities compartmentalize the nucleus into discrete chromosome territories and indicate commonalities in the mechanisms that regulate the spatial structure of the genome during mitosis and interphase.

| S-EPMC3431300 | biostudies-literature

Chromosome intermingling-the physical basis of chromosome organization in differentiated cells.

Project description:Chromosome territories (CTs) in higher eukaryotes occupy tissue-specific non-random three-dimensional positions in the interphase nucleus. To understand the mechanisms underlying CT organization, we mapped CT position and transcriptional changes in undifferentiated embryonic stem (ES) cells, during early onset of mouse ES cell differentiation and in terminally differentiated NIH3T3 cells. We found chromosome intermingling volume to be a reliable CT surface property, which can be used to define CT organization. Our results show a correlation between the transcriptional activity of chromosomes and heterologous chromosome intermingling volumes during differentiation. Furthermore, these regions were enriched in active RNA polymerase and other histone modifications in the differentiated states. These findings suggest a correlation between the evolution of transcription program in modifying CT architecture in undifferentiated stem cells. This leads to the formation of functional CT surfaces, which then interact to define the three-dimensional CT organization during differentiation.

| S-EPMC5603959 | biostudies-literature

Interphase Chromosome Flow-FISH.

Project description:A 2-day method using flow cytometry and FISH for interphase cells was developed to detect monosomy 7 cells in myelodysplastic syndrome patients. The method, Interphase Chromosome Flow-FISH (IC Flow-FISH), involves fixation of leukocytes from blood, membrane permeabilization, hybridization of cellular DNA with peptide nucleic acid probes with cells intact, and analysis by flow cytometry. Hundreds to thousands of monosomy 7 cells were consistently detected from 10-20 mL of blood in patients with monosomy 7. Proportions of monosomy 7 cells detected in IC Flow-FISH were compared with results from conventional cytogenetics; identification of monosomy 7 populations was verified with FACS; and patient and donor cells were mixed to test for sensitivity. IC Flow-FISH allows for detecting monosomy 7 without requiring bone marrow procurement or the necessity of metaphase spreads, and wider applications to other chromosomal abnormalities are in development.

| S-EPMC3471523 | biostudies-literature

Mitotic chromosome binding predicts transcription factor properties in interphase

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-01-25 | GSE119784 | GEO

Interphase chromosome structures of human cells.

Project description:Major intermediates of chromosome condensation in erythroleukemia K562 cells are presented. Interphase chromatin structures became visible after reversal of permeabilization. Large-scale chromatin structures and the development of individual interphase chromosomes were observed by fluorescence microscopy. In the linear arrangement the following major intermediates of K562 chromatin condensation could be distinguished: (1) the most decondensed chromatin veil, (2) chromatin ribbon, (3) chromatin funnel, a new intermediate regarded as the earliest visible form of interphase chromosomes, (4) chromatin body, (5) 300 nm chromatin fiber, (6) u, v, or s forms of chromosomes, and (7) linear chromosomes. The observations made in nuclei of K562 cells conform to the model of helical coil chromosome condensation.

| S-EPMC3233911 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data