scholarly journals Large-scale Chromatin Organization and the Localization of Proteins Involved in Gene Expression in Human Cells

2002 ◽  
Vol 50 (10) ◽  
pp. 1303-1312 ◽  
Author(s):  
Pernette J. Verschure ◽  
Ineke van der Kraan ◽  
Jorrit M. Enserink ◽  
Martijn J. Moné ◽  
Erik M.M. Manders ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Distribution ◽  
Large Scale ◽  
Interphase Nucleus ◽  
Functional Organization ◽  
Human Fibroblasts ◽  
Chromatin Organization ◽  
Condensed Chromatin ◽  
Chromosome Territories ◽  
Interchromatin Compartment

Compartmentalization of the interphase nucleus is an important element in the regulation of gene expression. Here we investigated the functional organization of the interphase nucleus of HeLa cells and primary human fibroblasts. The spatial distribution of proteins involved in transcription (TFIIH and RNA polymerase II) and RNA processing and packaging (hnRNP-U) were analyzed in relation to chromosome territories and large-scale chromatin organization. We present evidence that these proteins are present predominantly in the interchromatin space, inside and between chromosome territories, and are largely excluded by domains of condensed chromatin. We show that they are present throughout the active and inactive X-chromosome territories in primary female fibroblasts, indicating that these proteins can freely diffuse throughout the interchromatin compartment in the interphase nucleus. Furthermore, we established that the in vivo spatial distribution of condensed chromatin in the interphase nucleus does not depend on ongoing transcription. Our data support a conceptually simple model for the functional organization of interphase nuclei.

scholarly journals Single cell analysis reveals stochastic cell-to-cell variation in stress response and senescence program

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1055-1055
Author(s):  
Nikolay Burnaevskiy ◽  
Alexander Mendenhall
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Single Cell ◽  
Large Scale ◽  
Single Cell Analysis ◽  
Human Fibroblasts ◽  
Gene Expression Signature ◽  
Controlled Environment ◽  
Proliferating Cells ◽  
Expression Signature

Abstract Cells have various means to respond to molecular stress. Upon stress, proliferating cells can adopt different fates, e.g. commit to apoptosis, go into senescence or recover from stress and resume proliferation, depending on severity of the stress. Proper balance between these modes of response is critical for maintaining tissue homeostasis with age, as both exacerbated and insufficient response can result in pathology. Remarkably, even genetically identical cells of the same type in the controlled environment can exhibit a spectrum of responses to the same stress challenge. We hypothesized that analyzing response of individual cells in controlled environment can help better understand the mechanisms that ensure a balanced response to molecular stress. We used large scale single cell RNA-sequencing to analyze response of individual human fibroblasts to oxidative stress. Consistent with various fates adopted by individual cells upon stress, we observed different transcriptional signatures, that correspond to those fates. Surprisingly, when we specifically analyzed ß-gal+ senescent cells, we still observed transcriptional heterogeneity, with only a subset of cells exhibiting pro-senescent transcriptional signature (e.g. activated p53 and TNF-a pathways) while another subset exhibits a gene expression signature of senescent-like arrest. Hence, we find that in addition to known stress-related fates (apoptosis, senescence, recovery) senescence-like response is heterogeneous with only subset of cells exhibiting expected pro-senescent gene expression signature. Further characterization of heterogeneity of stress response and senescent-like fates will help better understand the mechanisms of homeostatic control in the face of molecular stress and aging.

scholarly journals Genes responsive to rapamycin and serum deprivation are clustered on chromosomes and undergo reorganization within local chromatin environments

2020 ◽  
Vol 98 (2) ◽  
pp. 178-190 ◽  
Author(s):  
Zachery R. Belak ◽  
Joshua. A. Pickering ◽  
Zoe. E. Gillespie ◽  
Gerald Audette ◽  
Mark Eramian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Fibroblasts ◽  
Chromosome Territory ◽  
Serum Deprivation ◽  
Chromosome Territories ◽  
Chromosome Conformation ◽  
Genome Reorganization ◽  
Intergenic Regions ◽  
Substantial Bias ◽  
Computational Analyses

We previously demonstrated that genome reorganization, through chromosome territory repositioning, occurs concurrently with significant changes in gene expression in normal primary human fibroblasts treated with the drug rapamycin, or stimulated into quiescence. Although these events occurred concomitantly, it is unclear how specific changes in gene expression relate to reorganization of the genome at higher resolution. We used computational analyses, genome organization assays, and microscopy, to investigate the relationship between chromosome territory positioning and gene expression. We determined that despite relocation of chromosome territories, there was no substantial bias in the proportion of genes changing expression on any one chromosome, including chromosomes 10 and 18. Computational analyses identified that clusters of serum deprivation and rapamycin-responsive genes along the linear extent of chromosomes. Chromosome conformation capture (3C) analysis demonstrated the strengthening or loss of specific long-range chromatin interactions in response to rapamycin and quiescence induction, including a cluster of genes containing Interleukin-8 and several chemokine genes on chromosome 4. We further observed that the LIF gene, which is highly induced upon rapamycin treatment, strengthened interactions with up- and down-stream intergenic regions. Our findings indicate that the repositioning of chromosome territories in response to cell stimuli, this does not reflect gene expression changes occurring within physically clustered groups of genes.

scholarly journals A Lamin Associated Chromatin Model for Chromosome Organization

2019 ◽  
Author(s):  
Ajoy Maji ◽  
Jahir Ahmed ◽  
Shubhankar Roy ◽  
Buddhapriya Chakrabarti ◽  
Mithun K. Mitra
Keyword(s):  
Gene Expression ◽  
Simple Model ◽  
Nuclear Membrane ◽  
Chromatin Organization ◽  
Chromosome Organization ◽  
Chromosome Territories ◽  
Polymer Model

We propose a simple model for chromatin organization based on the interaction of the chromatin fibres with Lamin proteins along the nuclear membrane. Lamin proteins are known to be a major factor that influences chromatin organization, and hence gene expression in the cells. Our polymer model explains the formation of lamin associated domains, and for heteropolymers with sequence control, can reproduce observed length distributions of LADs. In particular, lamin mediated interaction can enhance the formation of chromosome territories as well as the organization of chromatin into tightly packed heterochromatin and the loosely-packed gene-rich euchromatin regions.

Large-scale mapping of the catenas vegetation in Subarctic tundra

1995 ◽  
pp. 3-21
Author(s):  
S. S. Kholod
Keyword(s):  
Spatial Distribution ◽  
Vegetation Cover ◽  
Large Scale ◽  
Block Diagram ◽  
Abiotic Factors ◽  
Ecological Factors ◽  
Spatial Arrangement ◽  
Geological Time ◽  
Ecological Barriers ◽  
Functional Zones

One of the most difficult tasks in large-scale vegetation mapping is the clarification of mechanisms of the internal integration of vegetation cover territorial units. Traditional way of searching such mechanisms is the study of ecological factors controlling the space heterogeneity of vegetation cover. In essence, this is autecological analysis of vegetation. We propose another way of searching the mechanisms of territorial integration of vegetation. It is connected with intracoenotic interrelation, in particular, with the changing role of edificator synusium in a community along the altitudinal gradient. This way of searching is illustrated in the model-plot in subarctic tundra of Central Chukotka. Our further suggestion concerns the way of depicting these mechanisms on large-scale vegetation map. As a model object we chose the catena, that is the landscape formation including all geomorphjc positions of a slope, joint by the process of moving the material down the slope. The process of peneplanation of a mountain system for a long geological time favours to the levelling the lower (accumulative) parts of slopes. The colonization of these parts of the slope by the vegetation variants, corresponding to the lowest part of catena is the result of peneplanation. Vegetation of this part of catena makes a certain biogeocoenotic work which is the levelling of the small infralandscape limits and of the boundaries in vegetation cover. This process we name as the continualization on catena. In this process the variants of vegetation in the lower part of catena are being broken into separate synusiums. This is the process of decumbation of layers described by V. B. Sochava. Up to the slope the edificator power of the shrub synusiums sharply decreases. Moss and herb synusium have "to seek" the habitats similar to those under the shrub canopy. The competition between the synusium arises resulting in arrangement of a certain spatial assemblage of vegetation cover elements. In such assemblage the position of each element is determined by both biotic (interrelation with other coenotic elements) and abiotic (presence of appropriate habitats) factors. Taking into account the biogeocoenotic character of the process of continualization on catena we name such spatial assemblage an exolutionary-biogeocoenotic series. The space within each evolutionary-biogeocoenotic series is divided by ecological barriers into some functional zones. In each of the such zones the struggle between synusiums has its individual expression and direction. In the start zone of catena (extensive pediment) the interrelations of synusiums and layers control the mutual spatial arrangement of these elements at the largest extent. Here, as a rule, there predominate edificator synusiums of low and dwarfshrubs. In the first order limit zone (the bend of pediment to the above part of the slope) one-species herb and moss synusiums, oftenly substituting each other in similar habitats, get prevalence. In the zone of active colonization of slope (denudation slope) the coenotic factor has the least role in the spatial distribution of the vegetation cover elements. In particular, phytocoenotic interactions take place only within separate microcoenoses of herbs, mosses and lichens. In the zone of the attenuation of continualization process (the upper most parts of slope, crests) phytocoenotic interactions are almost absent and the spatial distribution of vegetation cover elements depends exclusively on the abiotic factors. The principal scheme of the distribution of vegetation cover elements and the disposition of functional zones on catena are shown on block-diagram (fig. 1).

Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Molecular Epidemiology ◽  
Exposure Assessment ◽  
Large Scale ◽  
First Generation ◽  
Cancer Epidemiology ◽  
Policy Changes ◽  
The Past ◽  
New Generation

The purpose of this review is to evaluate progress inmolecular epidemiology over the past 24 years in canceretiology and prevention to draw lessons for futureresearch incorporating the new generation of biomarkers.Molecular epidemiology was introduced inthe study of cancer in the early 1980s, with theexpectation that it would help overcome some majorlimitations of epidemiology and facilitate cancerprevention. The expectation was that biomarkerswould improve exposure assessment, document earlychanges preceding disease, and identify subgroupsin the population with greater susceptibility to cancer,thereby increasing the ability of epidemiologic studiesto identify causes and elucidate mechanisms incarcinogenesis. The first generation of biomarkers hasindeed contributed to our understanding of riskandsusceptibility related largely to genotoxic carcinogens.Consequently, interventions and policy changes havebeen mounted to reduce riskfrom several importantenvironmental carcinogens. Several new and promisingbiomarkers are now becoming available for epidemiologicstudies, thanks to the development of highthroughputtechnologies and theoretical advances inbiology. These include toxicogenomics, alterations ingene methylation and gene expression, proteomics, andmetabonomics, which allow large-scale studies, includingdiscovery-oriented as well as hypothesis-testinginvestigations. However, most of these newer biomarkershave not been adequately validated, and theirrole in the causal paradigm is not clear. There is a needfor their systematic validation using principles andcriteria established over the past several decades inmolecular cancer epidemiology.

scholarly journals Modeling Spatiotemporal Population Changes by Integrating DMSP-OLS and NPP-VIIRS Nighttime Light Data in Chongqing, China

2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Dan Lu ◽  
Yahui Wang ◽  
Qingyuan Yang ◽  
Kangchuan Su ◽  
Haozhe Zhang ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Relative Error ◽  
Urban Areas ◽  
Large Scale ◽  
Population Distribution ◽  
Spatial Optimization ◽  
Distribution Data ◽  
Mountainous Areas ◽  
Mean Relative Error ◽  
Nighttime Light

The sustained growth of non-farm wages has led to large-scale migration of rural population to cities in China, especially in mountainous areas. It is of great significance to study the spatial and temporal pattern of population migration mentioned above for guiding population spatial optimization and the effective supply of public services in the mountainous areas. Here, we determined the spatiotemporal evolution of population in the Chongqing municipality of China from 2000–2018 by employing multi-period spatial distribution data, including nighttime light (NTL) data from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP-OLS) and the Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS). There was a power function relationship between the two datasets at the pixel scale, with a mean relative error of NTL integration of 8.19%, 4.78% less than achieved by a previous study at the provincial scale. The spatial simulations of population distribution achieved a mean relative error of 26.98%, improved the simulation accuracy for mountainous population by nearly 20% and confirmed the feasibility of this method in Chongqing. During the study period, the spatial distribution of Chongqing’s population has increased in the west and decreased in the east, while also increased in low-altitude areas and decreased in medium-high altitude areas. Population agglomeration was common in all of districts and counties and the population density of central urban areas and its surrounding areas significantly increased, while that of non-urban areas such as northeast Chongqing significantly decreased.

scholarly journals The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Ekaterina Bourova-Flin ◽  
Samira Derakhshan ◽  
Afsaneh Goudarzi ◽  
Tao Wang ◽  
Anne-Laure Vitte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Specific Gene ◽  
Specific Expression ◽  
Intrinsic Nature ◽  
Independent Cohort

Abstract Background Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

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