scholarly journals Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants

2021 ◽  
Author(s):  
S Cole Kitzman ◽  
Tingting Duan ◽  
Miles A Pufall ◽  
Pamela K Geyer
Keyword(s):  
Gene Expression ◽  
Nuclear Lamina ◽  
Global Gene Expression ◽  
Regulation Of Transcription ◽  
Germline Stem Cells ◽  
General Role ◽  
Lamin B ◽  
Expression Of Genes ◽  
Dna Replication And Repair ◽  
Protein Barrier

Abstract The nuclear lamina (NL) lines the inner nuclear membrane. This extensive protein network organizes chromatin and contributes to the regulation of transcription, DNA replication and repair. Lap2-emerin-MAN1 domain (LEM-D) proteins are key members of the NL, representing proteins that connect the NL to the genome through shared interactions with the chromatin binding protein Barrier-to-autointegration factor (BAF). Functions of the LEM-D protein emerin and BAF are essential during Drosophila melanogaster oogenesis. Indeed, loss of either emerin or BAF blocks germ cell development and causes loss of germline stem cells, defects linked to deformation of NL structure and non-canonical activation of Checkpoint kinase 2 (Chk2). Here, we investigate contributions of emerin and BAF to gene expression in the ovary. Profiling RNAs from emerin and baf mutant ovaries revealed that nearly all baf mis-regulated genes were shared with emerin mutants, defining a set of NL-regulated genes. Strikingly, loss of Chk2 restored expression of most NL-regulated genes, identifying a large class of Chk2-dependent genes (CDGs). Nonetheless, some genes remained mis-expressed upon Chk2 loss, identifying a smaller class of emerin-dependent genes (EDGs). Properties of EDGs suggest a shared role for emerin and BAF in repression of developmental genes. Properties of CDGs demonstrate that Chk2 activation drives global mis-expression of genes in the emerin and baf mutant backgrounds. Notably, CDGs were found up-regulated in lamin-B mutant backgrounds. These observations predict that Chk2 activation might have a general role in gene expression changes found in NL-associated diseases, such as laminopathies.

scholarly journals Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa

2018 ◽  
Vol 115 (48) ◽  
pp. E11321-E11330 ◽  
Author(s):  
Jie Hou ◽  
Xiaowen Shi ◽  
Chen Chen ◽  
Md. Soliman Islam ◽  
Adam F. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Leaf Tissue ◽  
Global Gene Expression ◽  
Published Data ◽  
Chromosomal Imbalance ◽  
Regulatory Processes ◽  
Expression Of Genes ◽  
Global Impacts

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.

scholarly journals Role of Sigma Factors in Controlling Global Gene Expression in Light/Dark Transitions in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2007 ◽  
Vol 189 (21) ◽  
pp. 7829-7840 ◽  
Author(s):  
Tina C. Summerfield ◽  
Louis A. Sherman
Keyword(s):  
Gene Expression ◽  
Global Gene Expression ◽  
Growth Conditions ◽  
Day Length ◽  
Regulation Of Transcription ◽  
Wild Type ◽  
Protein Levels ◽  
In The Wild ◽  
Altered Gene ◽  
Pcc 6803

ABSTRACT We report on differential gene expression in the cyanobacterium Synechocystis sp. strain PCC 6803 after light-dark transitions in wild-type, ΔsigB, and ΔsigD strains. We also studied the effect of day length in the presence of glucose on a ΔsigB ΔsigE mutant. Our results indicated that the absence of SigB or SigD predominately altered gene expression in the dark or in the light, respectively. In the light, approximately 350 genes displayed transcript levels in the ΔsigD strain that were different from those of the wild type, with over 200 of these up-regulated in the mutant. In the dark, removal of SigB altered more than 150 genes, and the levels of 136 of these were increased in the mutant compared to those in the wild type. The removal of both SigB and SigE had a major impact on gene expression under mixotrophic growth conditions and resulted in the inability of cells to grow in the presence of glucose with 8-h light and 16-h dark cycles. Our results indicated the importance of group II σ factors in the global regulation of transcription in this organism and are best explained by using the σ cycle paradigm with the stochastic release model described previously (R. A. Mooney, S. A. Darst, and R. Landick, Mol. Cell 20:335-345, 2005). We combined our results with the total protein levels of the σ factors in the light and dark as calculated previously (S. Imamura, S. Yoshihara, S. Nakano, N. Shiozaki, A. Yamada, K. Tanaka, H. Takahashi, M. Asayama, and M. Shirai, J. Mol. Biol. 325:857-872, 2003; S. Imamura, M. Asayama, H. Takahashi, K. Tanaka, H. Takahashi, and M. Shirai, FEBS Lett. 554:357-362, 2003). Thus, we concluded that the control of global transcription is based on the amount of the various σ factors present and able to bind RNA polymerase.

scholarly journals Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pernille Barkholt ◽  
Kristoffer T. G. Rigbolt ◽  
Mechthilde Falkenhahn ◽  
Thomas Hübschle ◽  
Uwe Schwahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
Gene Expression Signature ◽  
Global Gene Expression ◽  
Metabolic Effects ◽  
Expression Of Genes ◽  
Hypothalamic Arcuate Nucleus ◽  
Laser Capture

Abstract The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

scholarly journals Effect of Bortezomib on Global Gene Expression in PC12-Derived Nerve Cells

2020 ◽  
Vol 21 (3) ◽  
pp. 751 ◽  
Author(s):  
Karolina Łuczkowska ◽  
Dorota Rogińska ◽  
Zofia Ulańczyk ◽  
Bogusław Machaliński
Keyword(s):  
Gene Expression ◽  
Mirna Expression ◽  
Global Gene Expression ◽  
Nerve Cells ◽  
Microarray Expression Data ◽  
Neurotransmitter Secretion ◽  
Dna Replication And Repair ◽  
Gene Correlation ◽  
Regulation Of Cell Cycle ◽  
Microarray Expression

Peripheral neuropathy is one of the main side-effects of novel therapeutics used in oncohematological diseases, but the molecular basis underlying its development and progression as well as neurotoxicity mechanisms induced by the use of these therapeutics are still not fully elucidated. The aim of this study was to demonstrate the effect of bortezomib on global gene and miRNA expression on PC12-derived nerve cells. Microarray analysis showed that expression of 1383 genes was downregulated at least two fold and 671 genes were upregulated at least two fold in PC12-derived nerve cells treated with bortezomib compared to untreated/control cells. Analysis of functional annotations mainly identified downregulated processes (e.g., regulation of cell cycle, DNA replication and repair, regulation of cell migration, neuron projection morphogenesis and neurotransmitter secretion). The result of miRNA expression analysis demonstrated only 11 significantly downregulated miRNAs (at least two fold) in bortezomib-treated PC12-derived nerve cells vs. control cells. MiRNAs regulate gene expression, therefore we decided to conduct an analysis comparing the outcomes of miRNA microarray expression data to the obtained mRNA data. The most interesting miRNA–target gene correlation is downregulated expression of miR-130a-3p and miR-152-3p and as a result of this downregulation the expression of the Gadd45 increased. This gene is a member of a group of genes, the transcript expression of which is enhanced after stressful growth arrest conditions and treatment with DNA-damaging agents like drugs or mutagens.

scholarly journals Impact of Chromosome Fusions on 3D Genome Organization and Gene Expression in Budding Yeast

Genetics ◽  
2020 ◽  
Vol 214 (3) ◽  
pp. 651-667 ◽  
Author(s):  
Marco Di Stefano ◽  
Francesca Di Giovanni ◽  
Vasilisa Pozharskaia ◽  
Mercè Gomar-Alba ◽  
Davide Baù ◽  
...  
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Nuclear Organization ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Global Gene Expression ◽  
3D Genome ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Chromosome Fusions

The three-dimensional (3D) organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remain debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization and global gene expression in budding yeast containing chromosome fusions. We used computational modeling and single-cell imaging to determine chromosome positions, and integrated these data with genome-wide transcriptional profiles from RNA sequencing. We find that chromosome fusions dramatically alter 3D nuclear organization without leading to strong genome-wide changes in transcription. However, we observe a mild but significant and reproducible increase in the expression of genes displaced away from the periphery. The increase in transcription is inversely proportional to the propensity of a given locus to be at the nuclear periphery; for example, a 10% decrease in the propensity of a gene to reside at the nuclear envelope is accompanied by a 10% increase in gene expression. Modeling suggests that this is due to both deletion of telomeres and to displacement of genes relative to the nuclear periphery. These data suggest that basal transcriptional activity is sensitive to radial changes in gene position, and provide insight into the functional relevance of budding yeast chromosome-level 3D organization in gene expression.

Gene Expression Profiling in AML and MDS Identifies Genes Located on 5q Which Are Consistently Lower Expressed in Cases with 5q Deletion as Compared to Cases with Normal Karyotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 549-549 ◽  
Author(s):  
Claudia Schoch ◽  
Alexander Kohlmann ◽  
Wolfgang Kern ◽  
Sylvia Merk ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Signal Transduction ◽  
Normal Karyotype ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Chromosome 5 ◽  
Expression Of Genes ◽  
Lower Expression ◽  
5Q Deletion

Abstract Deletions of the long arm of chromosome 5 occur either as the sole karyotype abnormality in MDS and AML or as part of a complex aberrant karyotype. It was the aim of this study to analyze the impact of the 5q deletion on the expression levels of genes located on chromosome 5q in AML and MDS. Therefore, gene expression analysis was performed in 344 AML and MDS cases using Affymetrix U133A+B oligonucleotide microarrays. The following subgroups were analyzed: AML with sole 5q deletion (n=7), AML with complex aberrant karyotype (n=83), MDS with sole 5q deletion (n=9), and MDS with complex aberrant karyotype (n=9). These were compared to 200 AML and 36 MDS with normal karyotype. In total, 1313 probe sets representing 603 genes cover sequences located on the long arm of chromosome 5. Overall a significant lower mean expression of all genes located on the long arm of chromosome 5 was observed in subgroups with 5q deletion in comparison to their respective control groups (for all comparisons, p<0.05). 36 genes showed a significantly lower expression in all comparisons. These genes are involved in a variety of different biological processes such as signal transduction (CSNK1A1, DAMS), cell cycle regulation (HDAC3, PFDN1) and regulation of transcription (CNOT8). In addition we performed class prediction using support vector machines (SVM). In one approach all 6 different subgroups were analyzed as one class each. While AML and MDS with normal karyotype as well as AML with complex aberrant karyotype were correctly predicted with high accuracies (97%, 81%, and 92%, respectively) AML and MDS with 5q- sole and MDS with complex aberrant karyotype were frequently misclassified as AML with complex aberrant karyotype. In a second approach only two classes were defined: all cases with 5q deletion combined vs. all cases without 5q deletion. 102 out of 108 cases (94%) with 5q deletion were identified correctly supporting the fact that a distinct gene expression pattern is associated with 5q deletion in general. Performing SVM only with genes located on the long arm of chromosome 5 also resulted in a correct prediction of 92 of 108 (85%) stressing the importance of the expression of genes located on chromosome 5 for these AML and MDS subtypes. The top 100 differentially expressed probe sets between cases with and without 5q deletion represented 74 different annotated genes of which 23 are located on the long arm of chromosome 5. They are involved in a variety of different biological functions such as DNA repair (POLE, RAD21, RAD23B), regulation of transcription (ZNF75A, AF020591, MLLT3, HOXB6), protein biosynthesis (UPF2, TINP1, RPL12, RPL14, RPL15) cell cycle control (GMNN, CSPG6, PFDN1) and signal transduction (HINT1, STK24, APP, CAMLG). 10 of the top 74 genes associated with 5q deletion were involved in the CMYC-pathway with upregulation of RAD21, RAD23B, GMMN, CSPG6, APP, POLE STK24 and STAG2, and downregulation of ACTA2, and RPL12. Ten other genes out of the 74 top differentially expressed genes were involved in the TP53 pathway with upregulation of H1F0, PTPN11 and TAF2 and downregulation of DF, UBE2D2, EEF1A1, IGBP1, PPP2CA, EIF2S3, and NACA. In conclusion, loss of parts of the long arm of chromosome 5 leads to a lower expression of genes located on the long arm of chromosome 5. A specific pattern of functionally related genes was identified which shows a lower expression in AML and MDS subtypes with 5q deletion.

scholarly journals Genomic dissection of the cytokine-controlled STAT5 signaling network in liver

2008 ◽  
Vol 34 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Atsushi Hosui ◽  
Lothar Hennighausen
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Target Genes ◽  
Global Gene Expression ◽  
Specific Expression ◽  
Partial Explanation ◽  
Downstream Target ◽  
Expression Of Genes ◽  
Global Gene Expression Profiling

Growth hormone (GH) controls the physiology and pathophysiology of the liver, and its signals are conducted by two members of the family of signal transducers and activators of transcription, STAT5A and STAT5B. Mice in which the Stat5a/b locus has been inactivated specifically in hepatocytes display GH resistance, the sex-specific expression of genes associated with liver metabolism and the cytochrome P-450 system is lost, and they develop hepatosteatosis. Several groups have shown by global gene expression profiling that a cadre of STAT5A/B target genes identify genetic cascades induced by GH and other cytokines. Evidence is accumulating that in the absence of STAT5A/B GH aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers a partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences: first, the failure of STAT5A/B target genes to be activated by GH and second, the rerouting of GH signaling to other members of the STAT family. Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B, but it certainly activates biological programs distinct from STAT5A/B. Here we discuss the extent to which studies on global gene expression profiling have fostered a better understanding of the biology behind cytokine-STAT5A/B networks in hepatocytes. We also explore whether this wealth of information on gene activity can be used to further understand the roles of cytokines in liver disease.

Transcriptomes reveal alterations in gravity impact circadian clocks and activate mechanotransduction pathways with adaptation through epigenetic change

2015 ◽  
Vol 47 (4) ◽  
pp. 113-128 ◽  
Author(s):  
Theresa Casey ◽  
Osman V. Patel ◽  
Karen Plaut
Keyword(s):  
Gene Expression ◽  
Late Pregnancy ◽  
Global Gene Expression ◽  
Circadian Clocks ◽  
Epigenetic Change ◽  
Pregnant Rats ◽  
Affymetrix Genechips ◽  
Expression Of Genes ◽  
The Impact

Few studies have investigated the impact of alterations in gravity on mammalian transcriptomes. Here, we describe the impact of spaceflight on mammary transcriptome of late pregnant rats and the effect of hypergravity exposure on mammary, liver, and adipose transcriptomes in late pregnancy and at the onset of lactation. RNA was isolated from mammary collected on pregnancy day 20 from rats exposed to spaceflight from days 11 to 20 of gestation. To measure the impact of hypergravity on mammary, liver, and adipose transcriptomes we isolated RNA from tissues collected on P20 and lactation day 1 from rats exposed to hypergravity beginning on pregnancy day 9. Gene expression was measured with Affymetrix GeneChips. Microarray analysis of variance revealed alterations in gravity affected the expression of genes that regulate circadian clocks and activate mechanotransduction pathways. Changes in these systems may explain global gene expression changes in immune response, metabolism, and cell proliferation. Expression of genes that modify chromatin structure and methylation was affected, suggesting adaptation to gravity alterations may proceed through epigenetic change. Altered gravity experiments offer insights into the role of forces omnipresent on Earth that shape genomes in heritable ways. Our study is the first to analyze the impact of alterations in gravity on transcriptomes of pregnant and lactating mammals. Findings provide insight into systems that sense gravity and the way in which they affect phenotype, as well as the possibility of sustaining life beyond Earth's orbit.

scholarly journals Endogenous retroviruses drive KRAB zinc-finger protein family expression for tumor suppression

2020 ◽  
Vol 6 (43) ◽  
pp. eabc3020 ◽  
Author(s):  
Jumpei Ito ◽  
Izumi Kimura ◽  
Andrew Soper ◽  
Alexandre Coudray ◽  
Yoshio Koyanagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zinc Finger ◽  
Tumor Suppression ◽  
Zinc Finger Protein ◽  
Global Gene Expression ◽  
Endogenous Retroviruses ◽  
Cellular Growth ◽  
Migration And Invasion ◽  
Cell Matrix ◽  
Expression Of Genes

Gene expression aberration is a hallmark of cancers, but the mechanisms underlying such aberrations remain unclear. Human endogenous retroviruses (HERVs) are genomic repetitive elements that potentially function as enhancers. Since numerous HERVs are epigenetically activated in tumors, their activation could cause global gene expression aberrations in tumors. Here, we show that HERV activation in tumors leads to the up-regulation of hundreds of transcriptional suppressors, namely, Krüppel-associated box domain–containing zinc-finger family proteins (KZFPs). KZFP genes are preferentially encoded nearby the activated HERVs in tumors and transcriptionally regulated by these adjacent HERVs. Increased HERV and KZFP expression in tumors was associated with better disease conditions. Increased KZFP expression in cancer cells altered the expression of genes related to the cell cycle and cell-matrix adhesion and suppressed cellular growth, migration, and invasion abilities. Our data suggest that HERV activation in tumors drives the synchronized elevation of KZFP expression, presumably leading to tumor suppression.

scholarly journals Slower development of lower canopy beans produces better coffee

2020 ◽  
Vol 71 (14) ◽  
pp. 4201-4214 ◽  
Author(s):  
Bing Cheng ◽  
Heather E Smyth ◽  
Agnelo Furtado ◽  
Robert J Henry
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Global Gene Expression ◽  
Coffee Production ◽  
High Quality ◽  
Development Stages ◽  
Expression Of Genes ◽  
Coffee Beans ◽  
The Impact ◽  
Selection Of

Abstract The production of high-quality coffee is being challenged by changing climates in coffee-growing regions. The coffee beans from the upper and lower canopy at different development stages of the same plants were analyzed to investigate the impact of the microenvironment on gene expression and coffee quality. Compared with coffee beans from the upper canopy, lower canopy beans displayed more intense aroma with higher caffeine, trigonelline, and sucrose contents, associated with greater gene expression in the representative metabolic pathways. Global gene expression indicated a longer ripening in the lower canopy, resulting from higher expression of genes relating to growth inhibition and suppression of chlorophyll degradation during early bean ripening. Selection of genotypes or environments that enhance expression of the genes slowing bean development may produce higher quality coffee beans, allowing coffee production in a broader range of available future environments.

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