scholarly journals Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Transition

2019 ◽  
Author(s):  
Haoyue Zhang ◽  
Daniel J. Emerson ◽  
Thomas G. Gilgenast ◽  
Katelyn R. Titus ◽  
Yemin Lan ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Extrusion Process ◽  
Domain Formation ◽  
Mitotic Chromosomes ◽  
Cis Element ◽  
Synchronous Cell ◽  
Kinetics Of ◽  
Contact Domain ◽  
Mitotic Chromatin ◽  
Time Point

AbstractHigher-order chromatin organization such as A/B compartments, TADs and chromatin loops are temporarily disrupted during mitosis. These structures are thought to organize aspects of gene regulation, and thus it is important to understand how they are re-established after mitosis. We examined the dynamics of chromosome reorganization by Hi-C at defined time points following exit from mitosis in highly purified, synchronous cell populations. We observed that A/B compartments are rapidly established and progressively gain in strength following mitotic exit. Contact domain formation occurs from the “bottom-up” with smaller sub-TADs forming initially, followed by convergence into multi-domain TAD structures. CTCF is strongly retained at a significant fraction of sites on mitotic chromosomes and immediately resumes full binding at ana/telophase, the earliest tested time point. In contrast, cohesin is completely evicted from mitotic chromosomes and resumes focal binding with delayed kinetics. The formation of CTCF/cohesin co-anchored structural loops follows the kinetics of cohesin positioning. Stripe-shaped contacts anchored by CTCF grow in length, consistent with a loop extrusion process after mitosis. Interactions between cis-regulatory elements can form rapidly, preceding CTCF/cohesin anchored structural loops. Strikingly, we identified a group of rapidly emerging transient contacts between cis-regulatory elements in ana/telophase, that are dissolved upon G1 entry, co-incident with the establishment of inner boundaries or nearby interfering loops. Our findings indicate that distinct but mutually influential forces drive post-mitotic chromatin re-configuration to shape compartments, contact domains, cis-element contacts, and CTCF/cohesin dependent loops.

scholarly journals Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins

2004 ◽  
Vol 168 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Danyang Chen ◽  
Miroslav Dundr ◽  
Chen Wang ◽  
Anthony Leung ◽  
Angus Lamond ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Repression ◽  
Core Histone ◽  
Mitotic Chromosomes ◽  
Chromatin Structural ◽  
Polymerase I ◽  
Kinetics Of ◽  
Mitotic Chromatin

During mitosis, chromosomes are highly condensed and transcription is silenced globally. One explanation for transcriptional repression is the reduced accessibility of transcription factors. To directly test this hypothesis and to investigate the dynamics of mitotic chromatin, we evaluate the exchange kinetics of several RNA polymerase I transcription factors and nucleosome components on mitotic chromatin in living cells. We demonstrate that these factors rapidly exchange on and off ribosomal DNA clusters and that the kinetics of exchange varies at different phases of mitosis. In addition, the nucleosome component H1c-GFP also shows phase-specific exchange rates with mitotic chromatin. Furthermore, core histone components exchange at detectable levels that are elevated during anaphase and telophase, temporally correlating with H3-K9 acetylation and recruitment of RNA polymerase II before the onset of bulk RNA synthesis at mitotic exit. Our findings indicate that mitotic chromosomes in general and ribosomal genes in particular, although highly condensed, are accessible to transcription factors and chromatin proteins. The phase-specific exchanges of nucleosome components during late mitotic phases are consistent with an emerging model of replication independent core histone replacement.

scholarly journals Spatial organization of transcript elongation and splicing kinetics

2021 ◽  
Author(s):  
Alyssa D. Casill ◽  
Adam J. Haimowitz ◽  
Brian Kosmyna ◽  
Charles C. Query ◽  
Kenny Ye ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Spatial Organization ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Multiple Control ◽  
Pol Ii ◽  
Topologically Associated Domains ◽  
Transcript Elongation ◽  
Kinetics Of

SummaryThe organization of the genome in three-dimensional space has been shown to play an important role in gene expression. Specifically, facets of genomic interaction such as topologically associated domains (TADs) have been shown to regulate transcription by bringing regulatory elements into close proximity1. mRNA production is an intricate process with multiple control points including regulation of Pol II elongation and the removal of non-coding sequences via pre-mRNA splicing2. The connection between genomic compartments and the kinetics of RNA biogenesis and processing has been largely unexplored. Here, we measure Pol II elongation and splicing kinetics genome-wide using a novel technique that couples nascent RNA-seq with a mathematical model of transcription and co-transcriptional RNA processing. We uncovered multiple layers of spatial organization of these rates: the rate of splicing is coordinated across introns within individual genes, and both elongation and splicing rates are coordinated within TADs, as are alternative splicing outcomes. Overall, our work establishes that the kinetics of transcription and splicing are coordinated by the spatial organization of the genome and suggests that TADs are a major platform for coordination of alternative splicing.

scholarly journals Influence of Plastic Deformation During Extrusion Process on Heat Resistance Alloys Fe40Al

2017 ◽  
Vol 62 (4) ◽  
pp. 2281-2286 ◽  
Author(s):  
D. Pasek ◽  
J. Cebulski
Keyword(s):  
Plastic Deformation ◽  
Heat Resistance ◽  
Structural Changes ◽  
Extrusion Process ◽  
Test Results ◽  
Research Setting ◽  
Alloy Matrix ◽  
X Ray ◽  
Kinetics Of ◽  
Corrosion Research

AbstractThe article presents the results of studies on the effects wrought on the corrosion resistance of the alloy matrix phase inter-metallic FeAl. Researches were carried out on the Fe40Al5Cr0.2TiB alloy and involved the oxidation of the samples after the crystallization after plastic deformation made by extrusion. The tests were performed in an oven in air at 1100°C for 100, 300 and 500 h. Determined to change the mass of the samples after corrosion research setting kinetics of corrosion processes, as well as an analysis of the microstructure of the alloy after the crystallization and after forming. The structure was examined using light microscopy and scanning electron microscopy and X-ray microanalysis with EDS chemical composition of the corrosion products. The test results revealed that plastic deformation during extrusion of intermetallic alloy led to structural changes, the effect of which was to improve the heat resistance at a temperature of 1100°C.

217 KINETICS OF SPERM PENETRATION IS CORRELATED WITH IN VITRO FERTILITY OF BUFFALO (BUBALUS BUBALIS) BULLS

2009 ◽  
Vol 21 (1) ◽  
pp. 206 ◽  
Author(s):  
M. Rubessa ◽  
M. Di Fenza ◽  
E. Mariotti ◽  
S. Di Francesco ◽  
C. de Dilectis ◽  
...  
Keyword(s):  
Bubalus Bubalis ◽  
Blastocyst Stage ◽  
Optimal Time ◽  
High Fertility ◽  
Chi Square ◽  
Sperm Penetration ◽  
Blastocyst Rate ◽  
Kinetics Of ◽  
Time Point

It was previously demonstrated that the kinetics of early cleavage could be used to discriminate between bovine bulls with high and low field fertility (Ward F et al. 2001 Mol. Reprod. Dev. 60, 47–55). Marked differences exist in the kinetics of sperm penetration between bulls, and this may be a useful predictor of field fertility in cattle (Ward F et al. 2002 Theriogenology 57, 2105–2117). It is well known that the ability to fertilize oocytes in vitro and to sustain embryo development varies significantly among buffalo bulls. Therefore, the aim of this work was to evaluate whether the speed of oocyte penetration after IVF was correlated with the blastocyst rates obtainable with different bulls in buffalo species. In Experiment 1, in vitro-matured buffalo oocytes were co-incubated with MitoTracker-labeled spermatozoa (Ward F et al. 2002 Theriogenology 57, 2105–2117) from 6 different bulls, over 2 replicates. Oocytes were subsequently fixed every 3 h (up to 18 h) postinsemination (pi). At each time point, oocytes were denuded, dezoned, fixed in ethanol overnight, and stained with 4′,6-diamidino-2-phenylindole for nuclei examination under a fluorescence microscope. In Experiment 2, in vitro-matured oocytes were fertilized with sperm from the same 6 bulls and were cultured to the blastocyst stage, over 4 replicates. Bulls were tested, collectively, on each batch of ovaries in both experiments. Differences in the percentages of monospermic penetration among bulls were analyzed by chi-square test. Correlation and multiple regression analyses were also carried out between the speed of penetration and blastocyst yields. Marked differences in the kinetics of sperm penetration were found among buffalo bulls, as shown in Table 1. Interestingly, a correlation was found between the blastocyst rate and the percentage of oocytes penetrated at 6 h (r = 0.71; P < 0.01), at 9 h (r = 0.65; P < 0.05), at 12 h (r = 0.77; P < 0.01), and at 18 h pi (r = 0.59; P < 0.05). Regression analysis showed that the optimal time of penetration for predicting the blastocyst rate was 12 h pi (R2 = 0.6). In conclusion, the kinetics of sperm penetration may be a useful marker to predict the in vitro-fertilizing ability of buffalo bulls. The great variability in the speed of oocyte penetration suggests inserting this assessment in the preliminary screening of bulls before their utilization in IVF programs. This may be helpful in selecting high-fertility bulls and identifying the optimal gamete co-incubation times for each bull used. Table 1.Percentage of oocytes penetrated at each time point (hpi, h postinsemination) by different bulls1

scholarly journals The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Cristina Ribeiro de Castro ◽  
Erick A. Barbosa ◽  
Renata P. Souza ◽  
Fabiana Agena ◽  
Patrícia S. de Souza ◽  
...  
Keyword(s):  
Acute Rejection ◽  
De Novo ◽  
First Year ◽  
Sharp Drop ◽  
Hla Antibodies ◽  
Single Antigen ◽  
The Impact ◽  
Kinetics Of ◽  
Time Point ◽  
Rejection Rates

The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed “de novo” Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, p<0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.

scholarly journals KIF4 helps mitotic chromosomes get in shape

2012 ◽  
Vol 199 (5) ◽  
pp. 715-715
Author(s):  
Ben Short
Keyword(s):  
Motor Protein ◽  
Mitotic Chromosomes ◽  
Kinesin Motor ◽  
Topoisomerase Iiα ◽  
Mitotic Chromatin

A kinesin motor protein works with condensin and topoisomerase IIα to organize mitotic chromatin.

scholarly journals Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes

Blood ◽  
2009 ◽  
Vol 113 (7) ◽  
pp. 1543-1546 ◽  
Author(s):  
Maria Diamandis ◽  
Andrew D. Paterson ◽  
Johanna M. Rommens ◽  
D. Kika Veljkovic ◽  
Jessica Blavignac ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Southern Blotting ◽  
Urokinase Plasminogen Activator ◽  
Regulatory Elements ◽  
Autosomal Dominant Disorder ◽  
Cis Element ◽  
Platelet Disorder ◽  
Function Defect ◽  
Upa Mrna ◽  
Platelet Content

Abstract Quebec platelet disorder (QPD) is an autosomal dominant disorder with high penetrance that is associated with increased risks for bleeding. The hallmark of QPD is a gain-of-function defect in fibrinolysis due to increased platelet content of urokinase plasminogen activator (uPA) without systemic fibrinolysis. We hypothesized that increased expression of uPA by differentiating QPD megakaryocytes is linked to PLAU. Genetic marker analyses indicated that QPD was significantly linked to a 2-Mb region on chromosome 10q containing PLAU with a maximum multipoint logarithm of the odds (LOD) score of +11 between markers D10S1432 and D10S1136. Analysis of PLAU by sequencing and Southern blotting excluded mutations within PLAU and its known regulatory elements as the cause of QPD. Analyses of uPA mRNA indicated that QPD distinctly increased transcript levels of the linked PLAU allele with megakaryocyte differentiation. These findings implicate a mutation in an uncharacterized cis element near PLAU as the cause of QPD.

Fluorescence-Based Measurement of Real-Time Kinetics of Protoporphyrin IX After 5-Aminolevulinic Acid Administration in Human In Situ Malignant Gliomas

Neurosurgery ◽  
2019 ◽  
Vol 85 (4) ◽  
pp. E739-E746 ◽  
Author(s):  
Sadahiro Kaneko ◽  
Eric Suero Molina ◽  
Christian Ewelt ◽  
Nils Warneke ◽  
Walter Stummer
Keyword(s):  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Protoporphyrin Ix ◽  
Time Dependency ◽  
Average Maximum ◽  
Kinetics Of ◽  
Acid Administration ◽  
Time Point

Abstract BACKGROUND Five-aminolevulinic acid (5-ALA) is well established for fluorescence-guided resections of malignant gliomas by eliciting the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. Because of the assumed time point of peak fluorescence, 5-ALA is recommended to be administered 3 h before surgery. However, the actual time dependency of tumor fluorescence has not yet been evaluated in humans and may have important implications. OBJECTIVE To investigate the time dependency of PpIX by measuring fluorescence intensities in tumors at various time points during surgery. METHODS Patients received 5-ALA (20 mg/kg b.w.) 3 to 4 h before surgery. Fluorescence intensities (FI) and estimated tumor PpIX concentrations (CPPIX) were measured in the tumors over time with a hyperspectral camera. CPPIX was assessed using hyperspectral imaging and by evaluating fluorescence phantoms with known CPPIX. RESULTS A total of 201 samples from 68 patients were included in this study. On average, maximum values of calculated FI and CPPIX were observed between 7 and 8 h after 5-ALA administration. FI and CPPIX both reliably distinguished central strong and marginal weak fluorescence, and grade III compared to grade IV gliomas. Interestingly, marginal (weak) fluorescence was observed to peak later than strong fluorescence (8-9 vs 7-8 h). CONCLUSION In human in Situ brain tumor tissue, we determined fluorescence after 5-ALA administration to be maximal later than previously thought. In consequence, 5-ALA should be administered 4 to 5 h before surgery, with timing adjusted to internal logistical circumstances and factors related to approaching the tumor.

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