scholarly journals Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

2019 ◽  
Author(s):  
Marion Cremer ◽  
Katharina Brandstetter ◽  
Andreas Maiser ◽  
Suhas S P Rao ◽  
Volker Schmid ◽  
...  
Keyword(s):  
Structural Changes ◽  
Nuclear Architecture ◽  
S Phase ◽  
Chromatin Domain ◽  
Channel System ◽  
3D Microscopy ◽  
Splicing Speckles ◽  
Spatio Temporal ◽  
Zonal Organization ◽  
Pass Through

AbstractCohesin plays an essential role in chromatin loop extrusion, but its impact on a compartmentalized nuclear architecture, linked to nuclear functions, is debatable. Using live-cell and super-resolved 3D microscopy, we demonstrate that cohesin depleted cells pass through an endomitosis and rebuild a single multilobulated nucleus (MLN) with chromosome territories (CTs) pervaded by interchromatin channels. CTs contain chromatin domain clusters with a zonal organization of repressed chromatin domains in the interior and transcriptionally competent domains located at the periphery. Splicing speckles are located nearby within the lining channel system. These clusters form microscopically defined, active and inactive compartments, which correspond to A/B compartments, detected with ensemble Hi-C. Functionality of MLN despite continuous absence of cohesin was demonstrated by their ability to pass through S-phase with typical spatio-temporal patterns of replication domains. Evidence for structural changes of these domains compared to controls suggests that cohesin is required for their full integrity.

scholarly journals Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Marion Cremer ◽  
Katharina Brandstetter ◽  
Andreas Maiser ◽  
Suhas S. P. Rao ◽  
Volker J. Schmid ◽  
...  
Keyword(s):  
Structural Changes ◽  
Nuclear Architecture ◽  
Human Colon ◽  
Chromatin Domain ◽  
Chromosome Territories ◽  
Human Colon Cancer ◽  
Splicing Speckles ◽  
Spatio Temporal ◽  
Zonal Organization ◽  
Pass Through

AbstractCohesin plays an essential role in chromatin loop extrusion, but its impact on a compartmentalized nuclear architecture, linked to nuclear functions, is less well understood. Using live-cell and super-resolved 3D microscopy, here we find that cohesin depletion in a human colon cancer derived cell line results in endomitosis and a single multilobulated nucleus with chromosome territories pervaded by interchromatin channels. Chromosome territories contain chromatin domain clusters with a zonal organization of repressed chromatin domains in the interior and transcriptionally competent domains located at the periphery. These clusters form microscopically defined, active and inactive compartments, which likely correspond to A/B compartments, which are detected with ensemble Hi-C. Splicing speckles are observed nearby within the lining channel system. We further observe that the multilobulated nuclei, despite continuous absence of cohesin, pass through S-phase with typical spatio-temporal patterns of replication domains. Evidence for structural changes of these domains compared to controls suggests that cohesin is required for their full integrity.

scholarly journals Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongzheng Li ◽  
Boxin Xue ◽  
Mengling Zhang ◽  
Liwei Zhang ◽  
Yingping Hou ◽  
...  
Keyword(s):  
Dna Replication ◽  
Structural Dynamics ◽  
Replication Origin ◽  
High Efficiency ◽  
S Phase ◽  
Chromatin Domain ◽  
Replication Origins ◽  
Replication Efficiency ◽  
Topologically Associating Domains ◽  
Epigenetic Signatures

Abstract Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

scholarly journals Developmental differences in genome replication program and origin activation

2020 ◽  
Vol 48 (22) ◽  
pp. 12751-12777
Author(s):  
Cathia Rausch ◽  
Patrick Weber ◽  
Paulina Prorok ◽  
David Hörl ◽  
Andreas Maiser ◽  
...  
Keyword(s):  
Dna Replication ◽  
Single Molecule ◽  
Embryonic Stem ◽  
S Phase ◽  
Developmental Differences ◽  
Centromeric Heterochromatin ◽  
Genome Replication ◽  
Origin Activation ◽  
Spatio Temporal ◽  
Mes Cells

Abstract To ensure error-free duplication of all (epi)genetic information once per cell cycle, DNA replication follows a cell type and developmental stage specific spatio-temporal program. Here, we analyze the spatio-temporal DNA replication progression in (un)differentiated mouse embryonic stem (mES) cells. Whereas telomeres replicate throughout S-phase, we observe mid S-phase replication of (peri)centromeric heterochromatin in mES cells, which switches to late S-phase replication upon differentiation. This replication timing reversal correlates with and depends on an increase in condensation and a decrease in acetylation of chromatin. We further find synchronous duplication of the Y chromosome, marking the end of S-phase, irrespectively of the pluripotency state. Using a combination of single-molecule and super-resolution microscopy, we measure molecular properties of the mES cell replicon, the number of replication foci active in parallel and their spatial clustering. We conclude that each replication nanofocus in mES cells corresponds to an individual replicon, with up to one quarter representing unidirectional forks. Furthermore, with molecular combing and genome-wide origin mapping analyses, we find that mES cells activate twice as many origins spaced at half the distance than somatic cells. Altogether, our results highlight fundamental developmental differences on progression of genome replication and origin activation in pluripotent cells.

scholarly journals The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

2021 ◽  
Vol 22 (11) ◽  
pp. 5483
Author(s):  
Luisa F. Bustamante-Jaramillo ◽  
Celia Ramos ◽  
Cristina Martín-Castellanos
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Cell Cycle Progression ◽  
Nuclear Architecture ◽  
Strand Break ◽  
Spindle Pole ◽  
S Phase ◽  
Cycle Progression ◽  
Single Wave ◽  
Phase Progression

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.

scholarly journals Structural Changes in Mcm5 Protein Bypass Cdc7-Dbf4 Function and Reduce Replication Origin Efficiency in Saccharomyces cerevisiae

2007 ◽  
Vol 27 (21) ◽  
pp. 7594-7602 ◽  
Author(s):  
Margaret L. Hoang ◽  
Ronald P. Leon ◽  
Luis Pessoa-Brandao ◽  
Sonia Hunt ◽  
M. K. Raghuraman ◽  
...  
Keyword(s):  
Structural Changes ◽  
S Phase ◽  
Minichromosome Maintenance ◽  
Chromosomal Replication ◽  
Origin Firing ◽  
Highly Active ◽  
Mcm Complex ◽  
Alternate States ◽  
Firing Efficiency ◽  
Intrinsic Firing

ABSTRACT Eukaryotic chromosomal replication is a complicated process with many origins firing at different efficiencies and times during S phase. Prereplication complexes are assembled on all origins in G1 phase, and yet only a subset of complexes is activated during S phase by DDK (for Dbf4-dependent kinase) (Cdc7-Dbf4). The yeast mcm5-bob1 (P83L) mutation bypasses DDK but results in reduced intrinsic firing efficiency at 11 endogenous origins and at origins located on minichromosomes. Origin efficiency may result from Mcm5 protein assuming an altered conformation, as predicted from the atomic structure of an archaeal MCM (for minichromosome maintenance) homologue. Similarly, an intragenic mutation in a residue predicted to interact with P83L suppresses the mcm5-bob1 bypass phenotype. We propose DDK phosphorylation of the MCM complex normally results in a single, highly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number of conformations, only one of which is permissive for origin activation. Random adoption of these alternate states by the mcm5-bob1 protein can explain both how origin firing occurs independently of DDK and why origin efficiency is reduced. Because similar mutations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the final target of DDK regulation.

scholarly journals Dinâmica Espaço-Temporal da Paisagem Semiárida no Município de Apodi/RN e seus Condicionantes Socioeconômicos e Ambientais

2021 ◽  
Vol 14 (4) ◽  
pp. 2446-2464
Author(s):  
Murianny Katamara Silva de Oliveira ◽  
Eveline Almeida Ferreira ◽  
Nadjacleia Vilar Almeida ◽  
Eulene Francisco da Silva ◽  
Aline Almeida Vasconcelos
Keyword(s):  
Vegetation Cover ◽  
Structural Changes ◽  
Temporal Dynamics ◽  
Agrarian Reform ◽  
Anthropogenic Activities ◽  
Standardized Precipitation Index ◽  
Environmental Drivers ◽  
Precipitation Data ◽  
Dense Vegetation ◽  
Spatio Temporal

Apodi, like many municipalities in the Northeast, underwent structural changes conducted by two main drivers: alternation of socioeconomic models and seasonal and prolonged periods of drought. Among the socioeconomic models, Apodi passed by large landowners, agrarian reform, expropriation of land for irrigated perimeters and installation of agribusiness companies. These conditions negatively impacted the vegetation cover, degrading the landscape and threatening the Lajedo de Soledade Archaeological Site (SALS) located in the middle of this landscape, an important cultural and environmental patrimony. In this context, the objective of this study was to analyze the spatio-temporal changes in the landscape around SALS and to infer about the influence of socioeconomic and environmental drivers. For this, a survey of the region's history, precipitation data, agricultural production of the main crops, and eight images captured by the TM and OLI sensors of the LANDSAT 5 and 8 satellites, between 1984 and 2018, were used. Precipitation data was modeled using the Standardized Precipitation Index (SPI). The images were classified using the SCP plugin (QGIS) and the quality was assessed using the Kappa Index. It was observed that there were three prolonged and extreme droughts events in the region: late 1980s and 1990s and between 2013 and 2017. The classification of the images indicated periods of dense vegetation reductions and exposed soil expansions, in the period of decay of cotton culture, and the reversal of these patterns after agrarian reform, with the establishment of family farming on an agroecological basis. This pattern was again reversed, with the lowest proportion of dense vegetation observed (5%) and and higher proportion of exposed soil (45%) observed in this landscape, during the period of installation of the irrigated perimeter for agribusiness. Thus, it was possible to infer that the alternation of socioeconomic models conditioned the spatio-temporal dynamics of the vegetation cover and was responsible for the environmental degradation conditions surrounding the SALS, these patterns being aggravated by the recurrence of periods of extreme and prolonged drought. During these periods, SALS was probably more vulnerable to the direct and indirect effects of anthropogenic activities common in this landscape.

Isotope Effect Studies on Elimination Reactions. XI. The Nature of the Transition State for the E2 Reaction of 2-Phenylethyldimethylanilinium Salts Containing Substituents in the Aniline Ring with Sodium Ethoxide in Ethanol

1975 ◽  
Vol 53 (23) ◽  
pp. 3513-3525 ◽  
Author(s):  
Peter Schmid ◽  
Arthur Newcombe Bourns
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Structural Changes ◽  
Isotope Effects ◽  
Sodium Ethoxide ◽  
Nitrogen Isotope ◽  
Structural Variations ◽  
Hydrogen Deuterium ◽  
Elimination Reactions ◽  
Pass Through

Kinetic isotope effects have been determined for the E2 reactions of a series of 2-phenylethyldimethylanilinium salts containing substituents in the aniline ring with sodium ethoxide in ethanol at 40 °C. The nitrogen isotope effect, (k14/k15−1)100, is not very sensitive to substituent changes but appears to increase slightly with increasing electron-withdrawing ability of the substituents, i.e., 1.19 ± 0.07, 1.13 ± 0.06, 1.12 ± 0.08, 1.30 ± 0.07, and 1.32 ± 0.06 for p-OCH3, p-CH3, p-H, p-Cl, and, m-CF3, respectively. The hydrogen–deuterium isotope effects pass through a minimum in the region of the unsubstituted compound and increase both with increasing electron-donating as well as with electron-withdrawing power of the substituents, i.e. kH/kD = 4.70 ± 0.06, 4.61 ± 0.04, 4.51 ± 0.04, 4.53 ± 0.09, 5.00 ± 0.07, and 5.39 ± 0.07 for p-OCH3, p-CH3, p-H, p-Cl, m-CF3, and p-CF3, respectively. The results are discussed in terms of recent theoretical treatments of the effect of structural variations in the reactants on the nature of the transition state of E2 elimination reactions. The conclusion is reached that the transition states in the present reaction series can be characterized as 'central with slight carbanion character' and that the effect of a change in the ability of the leaving group on the structure of the transition state manifests itself mainly in the direction perpendicular to the reaction coordinate. A simple novel hypothesis is formulated which emphasizes the importance of the location of the transition state in a More O'Ferrall-type potential energy diagram in determining its sensitivity to structural changes in the reactants.

S-phase-specific expression of the Mad3 gene in proliferating and differentiating cells

2001 ◽  
Vol 359 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Elizabeth J. FOX ◽  
Stephanie C. WRIGHT
Keyword(s):  
Cell Cycle ◽  
Cellular Proliferation ◽  
Cultured Cells ◽  
S Phase ◽  
Proliferating Cells ◽  
Specific Expression ◽  
Related Function ◽  
Erythroleukemia Cells ◽  
A Cell ◽  
Pass Through

The Myc/Max/Mad transcription factor network plays a central role in the control of cellular proliferation, differentiation and apoptosis. In order to elucidate the biological function of Mad3, we have analysed the precise temporal patterns of Mad3 mRNA expression during the cell cycle and differentiation in cultured cells. We show that Mad3 is induced at the G1/S transition in proliferating cells; expression persists throughout S-phase, and then declines as cells pass through G2 and mitosis. The expression pattern of Mad3 is coincident with that of Cdc2 throughout the cell cycle. In contrast, the expression of Mad3 during differentiation of cultured mouse erythroleukemia cells shows two transient peaks of induction. The first of these occurs at the onset of differentiation, and does not correlate with the S-phase of the cell cycle, whereas the second is coincident with the S-phase burst that precedes the terminal stages of differentiation. Our results therefore suggest that Mad3 serves a cell-cycle-related function in both proliferating and differentiating cells, and that it may also have a distinct role at various stages of differentiation.

scholarly journals Deriving Spatio-Temporal Geographies of Human Mobility from GPS traces

2021 ◽  
Author(s):  
Alessia Calafiore ◽  
Nombuyisielo Murage ◽  
Andrea Nasuto ◽  
Francisco Rowe
Keyword(s):  
Structural Changes ◽  
Human Mobility ◽  
Gps Data ◽  
Mobility Patterns ◽  
Individual Level ◽  
Temporal Properties ◽  
Detection Approach ◽  
Collective Movements ◽  
Spatio Temporal ◽  
City Structure

This paper leverages on the opportunities presented by individual level GPS data to study human mobility. It develops a methodology to understand the spatio-temporal properties of collective movements using network science. Through a spatially-weighted community detection approach, we derived functional neighbourhoods from human mobility patterns from GPS data and analyse the extent to which they vary across time. The results show that while the overall city structure remains stable, functional neighbourhoods tend to contract and expand over the course of the day. This work proposes a methodological framework and emphasises the importance of detecting short-term structural changes in cities based on human mobility.

scholarly journals Cell cycle progression and transmitotic apoptosis resistance promote escape from extrinsic apoptosis

2021 ◽  
Author(s):  
Nadine Pollak ◽  
Aline Lindner ◽  
Dirke Imig ◽  
Karsten Kuritz ◽  
Jacques S. Fritze ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Receptor Activation ◽  
S Phase ◽  
Apoptosis Resistance ◽  
Cycle Progression ◽  
Extrinsic Apoptosis ◽  
Primed State ◽  
Pass Through ◽  
Cycle Dependent

Extrinsic apoptosis relies on TNF-family receptor activation by immune cells or receptor-activating biologics. Here, we monitored cell cycle progression at minutes resolution to relate apoptosis kinetics and cell-to-cell heterogeneities in death decisions to cell cycle phases. Interestingly, we found that cells in S phase delay TRAIL receptor-induced death in favour for mitosis, thereby passing on an apoptosis-primed state to their offspring. This translates into two distinct fates, apoptosis execution post mitosis or cell survival from inefficient apoptosis. Transmitotic resistance is linked to Mcl-1 upregulation and increased accumulation at mitochondria from mid S phase onwards, which allows cells to pass through mitosis with activated caspase-8, and with cells escaping apoptosis after mitosis sustaining sublethal DNA damage. Antagonizing Mcl-1 suppresses cell cycle-dependent delays in apoptosis, prevents apoptosis-resistant progression through mitosis and averts unwanted survival from apoptosis induction. Cell cycle progression therefore modulates signal transduction during extrinsic apoptosis, with Mcl-1 governing decision making between death, proliferation and survival. Cell cycle progression thus is a crucial process from which cell-to-cell heterogeneities in fates and treatment outcomes emerge in isogenic cell populations during extrinsic apoptosis.

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