A nuclear glutathione cycle within the cell cycle

2010 ◽  
Vol 431 (2) ◽  
pp. 169-178 ◽  
Author(s):  
Pedro Diaz Vivancos ◽  
Tonja Wolff ◽  
Jelena Markovic ◽  
Federico V. Pallardó ◽  
Christine H. Foyer
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Nuclear Dna ◽  
Expression Patterns ◽  
Animal Cells ◽  
Cellular Redox ◽  
Intracellular Compartments ◽  
Glutathione Cycle ◽  
Defence Proteins ◽  
High Level

The complex antioxidant network of plant and animal cells has the thiol tripeptide GSH at its centre to buffer ROS (reactive oxygen species) and facilitate cellular redox signalling which controls growth, development and defence. GSH is found in nearly every compartment of the cell, including the nucleus. Transport between the different intracellular compartments is pivotal to the regulation of cell proliferation. GSH co-localizes with nuclear DNA at the early stages of proliferation in plant and animal cells. Moreover, GSH recruitment and sequestration in the nucleus during the G1- and S-phases of the cell cycle has a profound impact on cellular redox homoeostasis and on gene expression. For example, the abundance of transcripts encoding stress and defence proteins is decreased when GSH is sequestered in the nucleus. The functions of GSHn (nuclear GSH) are considered in the present review in the context of whole-cell redox homoeostasis and signalling, as well as potential mechanisms for GSH transport into the nucleus. We also discuss the possible role of GSHn as a regulator of nuclear proteins such as histones and PARP [poly(ADP-ribose) polymerase] that control genetic and epigenetic events. In this way, a high level of GSH in the nucleus may not only have an immediate effect on gene expression patterns, but also contribute to how cells retain a memory of the cellular redox environment that is transferred through generations.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

scholarly journals Plasticity of gene expression according to salinity in the testis of broodstock and F1 black-chinned tilapia, Sarotherodon melanotheron heudelotii

2014 ◽  
Author(s):  
Jean-Christophe Avarre ◽  
Bruno Guinand ◽  
Rémi Dugué ◽  
Jacky Cosson ◽  
Marc Legendre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Habitat ◽  
Expression Patterns ◽  
Osmotic Tolerance ◽  
Two Generations ◽  
Hypersaline Water ◽  
Significant Expression ◽  
Physiological Impact ◽  
High Level ◽  
Sarotherodon Melanotheron

The black-chinned tilapia Sarotherodon melanotheron heudelotii Rüppell 1852 (Teleostei, Cichlidae) displays remarkable acclimation capacities. When exposed to drastic changes of salinity, which can be the case in its natural habitat, it develops quick physiological responses and keeps reproducing. The present study focused on the physiological impact of salinity on male reproductive capacities, using gene expression as a proxy of acclimation process. Two series of experimental fish were investigated: the first one was composed of fish maintained in freshwater for several generations and newly acclimated to salinities of 35 and 70, whereas the second one consisted of the descendants of the latter born and raised under their native salinity. Expression patterns of 43 candidate genes previously identified from the testes of wild males was investigated in the three salinities and two generations. Twenty of them showed significant expression differences between salinities, and their predicted function revealed that most of them are involved in the osmotic tolerance of sperm cells and/or in the maintenance of sperm motility. A high level of expression variation was evidenced, especially for fish maintained in freshwater. In spite of this, gene expression patterns allowed the differentiation between fish raised in freshwater and those maintained in hypersaline water, in both generations. Altogether, the results presented here suggest that this high variability of expression is likely to ensure the reproductive success of this species under varying salinities.

Abstract 18584: Decoding the Regulatory LncRNAs in Neonatal Heart During Perinatal Circulatory Transition

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Marlin Touma ◽  
Ashley Cass ◽  
Xuedong Kang ◽  
Yan Zhao ◽  
Reshma Biniwale ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Regulatory Function ◽  
Newborn Mouse ◽  
Protein Coding ◽  
Congenital Diseases ◽  
Gene Pairs ◽  
Neonatal Heart

Background: Fetal to neonatal transition of heart is an elaborate process, during which, neonatal cardiomyocytes undergo functional maturation and terminal exit from the cell cycle. However, transcriptome programming in neonatal cardiac chambers during perinatal stages is understudied. In particular, the changes in long non-coding RNAs (lncRNAs) in neonatal heart have not been explored. Objective: To achieve transcriptome-wide analysis of lncRNAs in neonatal left ventricle (LV) and right ventricle (RV) during maturation stages using deep RNA-Sequencing Methods: Deep RNA-sequencing was performed on male newborn mouse (C57 BL) LV and RV at 3 time points of perinatal circulatory transition: P0, P3 and P7. Reads were mapped to mouse genome (mm10). The lncRNAs annotated in NONCODE database were identified. Differentially expressed lncRNAs were defined as those with coefficient of variation ≥0.2, at a false discovery rate ≤0.05, and expressed at ≥3 RPKM in at least one sample. Correlated lncRNAs/ gene pairs were identified using Pearson’s (r2≥0.8, P≤0.05). A subset of LncRNAs/gene expression was validated using qRT-PCR. Results: Out of the 70, 983 observed unique lncRNAs, approximately 7000 were identified exhibiting significant variation during maturation windows with highly spatial-temporal dependent expression patterns, including approximately 5000 known and 2000 novel lncRNAs. Notably, 20% of these lncRNAs were located within 50 KB of a protein coding gene. Out of a total of 2400 lncRNAs/gene pairs, 10 % exhibited significantly concordant (lncRNA/gene) expression patterns. These correlated genes were significantly enriched in metabolism, cell cycle and contractility functional ontology. Interestingly, some of these lncRNAs exhibited concordance with their neighboring gene in human tissues with congenital heart defects, suggesting conserved, potentially significant, regulatory function. Conclusions: Transcriptome programming during neonatal heart maturation involves global changes in lncRNAs. Their expression concordance with neighboring protein coding genes implicates potential important regulatory role of lncRNAs in neonatal heart chamber specification and congenital diseases.

scholarly journals Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells

2005 ◽  
Vol 34 (1) ◽  
pp. 61-75 ◽  
Author(s):  
F Gadal ◽  
A Starzec ◽  
C Bozic ◽  
C Pillot-Brochet ◽  
S Malinge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Data Analysis ◽  
Differential Expression ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Cycle Progression

To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast cancer cell growth, we investigated gene expression changes in MCF7 cells treated with 17β-estradiol (E2) and/or with 4-OH-TAM. The patterns of differential expression were determined by the ValiGen Gene IDentification (VGID) process, a subtractive hybridization approach combined with microarray validation screening. Their possible biologic consequences were evaluated by integrative data analysis. Over 1000 cDNA inserts were isolated and subsequently cloned, sequenced and analyzed against nucleotide and protein databases (NT/NR/EST) with BLAST software. We revealed that E2 induced differential expression of 279 known and 28 unknown sequences, whereas TAM affected the expression of 286 known and 14 unknown sequences. Integrative data analysis singled out a set of 32 differentially expressed genes apparently involved in broad cellular mechanisms. The presence of E2 modulated the expression patterns of 23 genes involved in anchors and junction remodeling; extracellular matrix (ECM) degradation; cell cycle progression, including G1/S check point and S-phase regulation; and synthesis of genotoxic metabolites. In tumor cells, these four mechanisms are associated with the acquisition of a motile and invasive phenotype. TAM partly reversed the E2-induced differential expression patterns and consequently restored most of the biologic functions deregulated by E2, except the mechanisms associated with cell cycle progression. Furthermore, we found that TAM affects the expression of nine additional genes associated with cytoskeletal remodeling, DNA repair, active estrogen receptor formation and growth factor synthesis, and mitogenic pathways. These modulatory effects of E2 and TAM upon the gene expression patterns identified here could explain some of the mechanisms associated with the acquisition of a more aggressive phenotype by breast cancer cells, such as E2-independent growth and TAM resistance.

scholarly journals Plasticity of gene expression according to salinity in the testis of broodstock and F1 black-chinned tilapia, Sarotherodon melanotheron heudelotii

2014 ◽  
Author(s):  
Jean-Christophe Avarre ◽  
Bruno Guinand ◽  
Rémi Dugué ◽  
Jacky Cosson ◽  
Marc Legendre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Habitat ◽  
Expression Patterns ◽  
Osmotic Tolerance ◽  
Two Generations ◽  
Hypersaline Water ◽  
Significant Expression ◽  
Physiological Impact ◽  
High Level ◽  
Sarotherodon Melanotheron

The black-chinned tilapia Sarotherodon melanotheron heudelotii Rüppell 1852 (Teleostei, Cichlidae) displays remarkable acclimation capacities. When exposed to drastic changes of salinity, which can be the case in its natural habitat, it develops quick physiological responses and keeps reproducing. The present study focused on the physiological impact of salinity on male reproductive capacities, using gene expression as a proxy of acclimation process. Two series of experimental fish were investigated: the first one was composed of fish maintained in freshwater for several generations and newly acclimated to salinities of 35 and 70, whereas the second one consisted of the descendants of the latter born and raised under their native salinity. Expression patterns of 43 candidate genes previously identified from the testes of wild males was investigated in the three salinities and two generations. Twenty of them showed significant expression differences between salinities, and their predicted function revealed that most of them are involved in the osmotic tolerance of sperm cells and/or in the maintenance of sperm motility. A high level of expression variation was evidenced, especially for fish maintained in freshwater. In spite of this, gene expression patterns allowed the differentiation between fish raised in freshwater and those maintained in hypersaline water, in both generations. Altogether, the results presented here suggest that this high variability of expression is likely to ensure the reproductive success of this species under varying salinities.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that modulates and maintains patterns of gene expression through the cell cycle

2020 ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

ABSTRACTBackgroundChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear.To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL) to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3.ResultsChromosome regions (bands) of 10-50Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. We show that they comprise 1-5Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely.We found little change between cell cycle phases, whether compared by 5Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains.Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription.ConclusionsModified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

High level analysis of genomic data reveals complex predictors of response to trastuzumab (T) and chemotherapy for early stage breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 544-544
Author(s):  
L. N. Harris ◽  
S. Carter ◽  
F. You ◽  
A. Eklund ◽  
S. Hilsenbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Pathologic Complete Response ◽  
Gene Expression Signature ◽  
Response To Therapy ◽  
Snp Analysis ◽  
Predictors Of Response ◽  
High Level

544 Background: Trastuzumab (T) with chemotherapy has been shown to improve survival in breast cancer patients but de novo resistance is common. Identifying predictors of response to T in primary cancers may lead to an understanding of mechanisms of resistance. We investigated whether combined microarray datasets from patients with early breast cancer treated with preoperative T and chemotherapy could predict for response to therapy. Methods: Two cohorts of patients with HER2 3+/FISH+, stage II-III breast cancer were included in this analysis: trial 1- T and docetaxel (n=38), trial 2 -T and vinorelbine (n=48), both for 12 weeks. Frozen tissue core biopsies were available and successfully amplified in 41 patients (trial 1: 20, trial 2: 21 patients), with standard sample processing, RNA extraction, amplification and hybridization to Affymetrix U133 chips. Differential expression of genes and chromosomal regions, (defined as >10 genes in a given chromosomal cytoband), between patients with pathologic complete response (pCR) vs. those with residual invasive disease were examined. A measure of total functional aneuploidy (tFA) was calculated by summing net deviation in expression of all chromosomal regions and a gene expression signature of genomic instability (CIN) was derived by the identification of genes showing a high level of correlation with tFA . Results: By unsupervised hierarchical analysis, both datasets interdigitated suggesting no inherent bias. Gene expression patterns of individual genes showed weak associations with pCR. However, distinct statistically significant chromosomal regions, Chr2p23 Chr6q24 Chr7q33 Chr2p2 Chr12q21.31 Chr14q32.2 Chr1p34.2 Chr8q21.3, were associated with pCR to T therapy (p<0.005), and were confirmed in more than 50% samples by SNP analysis. In addition, resistant tumors showed higher levels of the CIN signature (p<0.005). Conclusions: We have shown that gene expression data can be merged and used for discovery predictive chromosomal regions associated T response. In addition, chromosomal instability was associated with T resistance. If validated, these distinct dysregulated chromosomal regions may serve as predictive markers of response to trastuzumab therapy. [Table: see text]

Evolution of Gene Expression Signatures in Relapsed Childhood Acute Lymphoblastic Leukemia Differs Based on Timing of Relapse.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3345-3345
Author(s):  
Deepa Bhojwani ◽  
Jinhua Wang ◽  
Jun J Yang ◽  
Debra Morrison ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Expression Patterns ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Late Relapse ◽  
Gene Expression Patterns ◽  
Early Relapse ◽  
Over Expression

Abstract The outcome for childhood acute lymphoblastic leukemia (ALL) following marrow relapse remains bleak in spite of numerous approaches to further intensify therapy. Understanding the biological basis of relapse and chemoresistance, as well as identifying and validating potential new targets, are the goals of our study. Previously we determined global gene expression patterns of matched diagnosis and relapse leukemic blasts in 32 patients (64 samples) with childhood B-precursor ALL using Affymetrix U133A arrays (Blood2006;108(2):711–7). We now have extended this analysis to 60 patients (120 samples). Thirty-six patients relapsed early (within 36 months of initial diagnosis), while 24 patients relapsed late. Within the TEL/AML1 subset (n=12 patients), time to relapse was inversely proportional to the correlation co-efficient of expression profiles of the diagnosis and relapse matched pair samples, suggesting that the later the relapse, the more distinct the relapse clone is from the diagnostic clone. A supervised pairwise analysis in all 60 patients identified 292 probesets that were differentially expressed between diagnosis and relapse (FDR < 10%). In a relative enrichment analysis, multiple genes mediating cell death were down-regulated at relapse (p=0.00003), suggesting that the leukemia cells had evolved mechanisms to enhance survival. These included p21, TNFPAI3, RIPK2, BCLAF1, STK17B. In concert, DNA replication genes were up-regulated at relapse (p=0.00002). Differences in pathways leading to early vs. late relapse were evident. Early relapse was characterized by an over-expression of cell cycle genes reflecting a proliferative state. At the time of relapse, a marked over-representation of genes involved in the progression through the M phase of the cell cycle was observed in early relapse compared to late relapse (p=1.3E-08). Late relapse was characterized by the over-expression of genes involved in nucleoside biosynthesis, particularly targets of antifolates (DHFR, MTHFD1, TYMS). A small number of gene expression patterns were common to both early and late relapse, including up-regulation at relapse of BIRC5 (survivin): an attractive target for therapeutic intervention. In conclusion, analysis of an expanded cohort of matched diagnosis/relapse pairs has validated and extended our previous findings that early relapse is associated with a proliferative gene expression signature. In addition we have now identified pathways operative in late relapse. Targeting these individual genes and pathways may lead to innovative strategies to treat or prevent relapsed ALL.

scholarly journals Tumor-specific and Proliferation-specific Gene Expression Typifies Murine Transgenic B Cell Lymphomagenesis

2006 ◽  
Vol 282 (7) ◽  
pp. 4803-4811 ◽  
Author(s):  
Marc E. Lenburg ◽  
Anupama Sinha ◽  
Douglas V. Faller ◽  
Gerald V. Denis
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Cellular Proliferation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Specific Pattern ◽  
Specific Gene

The dual bromodomain protein Brd2 is closely related to the basal transcription factor TAFII250, which is essential for cyclin A transactivation and mammalian cell cycle progression. In transgenic mice, constitutive lymphoid expression of Brd2 causes a malignancy most similar to human diffuse large B cell lymphoma. We compare the genome-wide transcriptional expression profiles of these lymphomas with those of proliferating and resting normal B cells. Transgenic tumors reproducibly show differential expression of a large number of genes important for cell cycle control and lymphocyte biology; expression patterns are either tumor-specific or proliferation-specific. Several of their human orthologs have been implicated in human lymphomagenesis. Others correlate with human disease survival time. BRD2 is underexpressed in some subtypes of human lymphoma and these subtypes display a number of similarities to the BRD2-mediated murine tumors. We illustrate with a high degree of detail that cancer is more than rampant cellular proliferation, but involves the additional transcriptional mobilization of many genes, some of them poorly characterized, which show a tumor-specific pattern of gene expression.

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