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.

scholarly journals Impact of chromosome fusions on 3D genome organization and gene expression in budding yeast

2017 ◽  
Author(s):  
Marco Di Stefano ◽  
Francesca Di Giovanni ◽  
Davide Baù ◽  
Lucas B. Carey ◽  
Marc A. Marti-Renom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Nuclear Organization ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Computational Modelling ◽  
Global Gene Expression ◽  
3D Genome ◽  
Genome Wide ◽  
Chromosome Fusions

ABSTRACTThe three-dimensional organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remains 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 modelling and single cell imaging to determine chromosome position 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 expression of genes near fusion sites. Modeling suggests that this is due to both disruption of telomere-associated silencing and the displacement of genes relative to the nuclear periphery. A 10% decrease in the predicted time a gene spends near the nuclear periphery is associated with a 10% increase in expression. These data suggest that basal transcriptional activity is sensitive to radial changes on gene position, and provide insight into the functional relevance of budding yeast chromosome-level three-dimensional organization in gene expression.

scholarly journals Genome-Wide Analysis of the Relationship between Transcriptional Regulation by Rpd3p and the Histone H3 and H4 Amino Termini in Budding Yeast

2004 ◽  
Vol 24 (20) ◽  
pp. 8823-8833 ◽  
Author(s):  
Nevin Sabet ◽  
Sam Volo ◽  
Cailin Yu ◽  
James P. Madigan ◽  
Randall H. Morse
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Histone H3 ◽  
Global Gene Expression ◽  
Amino Terminus ◽  
Histone H4 ◽  
Histone Tails ◽  
Genome Wide ◽  
Lysine Residues ◽  
The Relationship

ABSTRACT The histone amino termini have emerged as key targets for a variety of modifying enzymes that function as transcriptional coactivators and corepressors. However, an important question that has remained largely unexplored is the extent to which specific histone amino termini are required for the activating and repressive functions of these enzymes, Here we address this issue by focusing on the prototypical histone deacetylase, Rpd3p, in the budding yeast Saccharomyces cerevisiae. We show that targeting Rpd3p to a reporter gene in this yeast can partially repress transcription when either the histone H3 or the histone H4 amino terminus is deleted, indicating that the “tails” are individually dispensable for repression by Rpd3p. In contrast, we find that the effect of rpd3 gene disruption on global gene expression is considerably reduced in either a histone H3Δ1-28 (H3 lacking the amino-terminal 28 amino acids) or a histone H4(K5,8,12,16Q) (H4 with lysine residues 5, 8, 12, and 16 changed to glutamine residues) background compared to the wild-type background, indicating a requirement for one or both of these histone tails in Rpd3p-mediated regulation for many genes. These results suggest that acetylation of either the H3 or the H4 amino terminus could suffice to allow the activation of such genes. We also examine the relationship between H3 tails and H4 tails in global gene expression and find substantial overlap among the gene sets regulated by these histone tails. We also show that the effects on genome-wide expression of deleting the H3 or H4 amino terminus are similar but not identical to the effects of mutating the lysine residues in these same regions. These results indicate that the gene regulatory potential of the H3 and H4 amino termini is substantially but not entirely contained in these modifiable lysine residues.

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 Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

2017 ◽  
Author(s):  
Cristina Cruz ◽  
Monica Della Rosa ◽  
Christel Krueger ◽  
Qian Gao ◽  
Lucy Field ◽  
...  
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Histone H3 ◽  
Specific Factor ◽  
Protein Coding ◽  
Replicative Lifespan ◽  
Protein Coding Genes ◽  
Genome Wide ◽  
Normal Expression ◽  
Transcriptional Induction

AbstractTranscription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.

scholarly journals Functional Comparison of the Tup11 and Tup12 Transcriptional Corepressors in Fission Yeast

2005 ◽  
Vol 25 (2) ◽  
pp. 716-727 ◽  
Author(s):  
Fredrik Fagerström-Billai ◽  
Anthony P. H. Wright
Keyword(s):  
Gene Expression ◽  
Gene Duplication ◽  
Fission Yeast ◽  
Budding Yeast ◽  
Functional Difference ◽  
Evolutionary Mechanism ◽  
Genome Wide ◽  
Number Of Genes ◽  
Transcriptional Corepressors ◽  
Genome Wide Gene Expression

ABSTRACT Gene duplication is considered an important evolutionary mechanism. Unlike many characterized species, the fission yeast Schizosaccharomyces pombe contains two paralogous genes, tup11 + and tup12 + , that encode transcriptional corepressors similar to the well-characterized budding yeast Tup1 protein. Previous reports have suggested that Tup11 and Tup12 proteins play redundant roles. Consistently, we show that the two Tup proteins can interact together when expressed at normal levels and that each can independently interact with the Ssn6 protein, as seen for Tup1 in budding yeast. However, tup11 − and tup12 − mutants have different phenotypes on media containing KCl and CaCl2. Consistent with the functional difference between tup11 − and tup12 − mutants, we identified a number of genes in genome-wide gene expression experiments that are differentially affected by mutations in the tup11 + and tup12 + genes. Many of these genes are differentially derepressed in tup11 − mutants and are over-represented in genes that have previously been shown to respond to a range of different stress conditions. Genes specifically derepressed in tup12 − mutants require the Ssn6 protein for their repression. As for Tup12, Ssn6 is also required for efficient adaptation to KCl- and CaCl2-mediated stress. We conclude that Tup11 and Tup12 are at least partly functionally diverged and suggest that the Tup12 and Ssn6 proteins have adopted a specific role in regulation of the stress response.

scholarly journals Histone H3K9 methylation promotes formation of genome compartments inCaenorhabditis elegansvia chromosome compaction and perinuclear anchoring

2020 ◽  
Vol 117 (21) ◽  
pp. 11459-11470 ◽  
Author(s):  
Qian Bian ◽  
Erika C. Anderson ◽  
Qiming Yang ◽  
Barbara J. Meyer
Keyword(s):  
Gene Expression ◽  
Nuclear Periphery ◽  
Chromosome Conformation ◽  
C Elegans ◽  
Genome Wide ◽  
Central Regions ◽  
In Trans ◽  
Genomic Regions ◽  
In Cis ◽  
Gene Expression Levels

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization inCaenorhabditis elegansand investigate roles for compartments in regulating gene expression. Distal arms ofC. eleganschromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other bothin cisandin trans,while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genesmet-2andset-25significantly impaired formation of inactive Arm and active Center compartments.cec-4mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote theircisassociation, and an anchoring-independent mechanism that compacts individual chromosome arms. In bothmet-2 set-25andcec-4mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.

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 Adenine DNA methylation, 3D genome organization, and gene expression in the parasiteTrichomonas vaginalis

2020 ◽  
Vol 117 (23) ◽  
pp. 13033-13043
Author(s):  
Ayelen Lizarraga ◽  
Zach Klapholz O’Brown ◽  
Konstantinos Boulias ◽  
Lara Roach ◽  
Eric Lieberman Greer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Trichomonas Vaginalis ◽  
Three Dimensional ◽  
Wide Distribution ◽  
Spatial Proximity ◽  
Regulation Of Transcription ◽  
3D Genome ◽  
Intergenic Regions ◽  
Close Spatial Proximity

Trichomonas vaginalisis a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5‐methylcytosine (5mC), is the main DNA methylation mark inT. vaginalis. Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA inT. vaginalisis associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.

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.

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