scholarly journals A genome-wide transcriptional analysis of morphology determination inCandida albicans

2013 ◽  
Vol 24 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Gene Expression ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Transcriptional Analysis ◽  
Specific Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genetically Manipulated

Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.

scholarly journals Genome-wide transcriptional profiling uncovers a similar oligodendrocyte-related transcriptional response to acute and chronic alcohol drinking in the amygdala

2021 ◽  
Author(s):  
Sharvari Narendra ◽  
Claudia Klengel ◽  
Bilal Hamzeh ◽  
Drasti Patel ◽  
Joy Otten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Drinking ◽  
Brain Area ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Histone Deacetylation ◽  
Regulatory Pathways ◽  
Genome Wide ◽  
A Genome

AbstractAlcohol intake progressively increases after prolonged consumption of alcohol, but relatively few new therapeutics targeting development of alcohol use disorder (AUD) have been validated. Here, we conducted a genome-wide RNA-sequencing (RNA-seq) analysis in mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in the amygdala including the central and basolateral subnuclei, a brain area previously implicated in alcohol drinking and seeking, demonstrating distinct gene expression patterns and canonical pathways induced by both acute and chronic intake. Surprisingly, both drinking modes triggered similar transcriptional changes, including up-regulation of ribosome-related/translational pathways and myelination pathways, and down-regulation of chromatin binding and histone modification. Notably, multiple genes that were significantly regulated in mouse amygdala with alcohol drinking, including Atp2b1, Slc4a7, Nfkb1, Nts, and Hdac2, among others had previously been associated with human AUD via GWAS or other genomic studies. In addition, analyses of hub genes and upstream regulatory pathways predicted that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and oligodendrocyte-related transcriptional factor, Sox17.Overall, our results suggest that the transcriptional landscape in the central and basolateral subnuclei of the amygdala is sensitive to voluntary alcohol drinking. They provide a unique resource of gene expression data for future translational studies examining transcriptional mechanisms underlying the development of AUD due to alcohol consumption.

A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Submandibular Salivary Gland ◽  
Data Sets ◽  
Control Mechanisms ◽  
Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

scholarly journals Limit cycle dynamics can guide the evolution of gene regulatory networks towards point attractors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stuart P. Wilson ◽  
Sebastian S. James ◽  
Daniel J. Whiteley ◽  
Leah A. Krubitzer
Keyword(s):  
Gene Expression ◽  
Limit Cycles ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Specific Gene ◽  
Boolean Models ◽  
A Genome ◽  
Order Of Magnitude ◽  
Accelerate Evolution

AbstractDevelopmental dynamics in Boolean models of gene networks self-organize, either into point attractors (stable repeating patterns of gene expression) or limit cycles (stable repeating sequences of patterns), depending on the network interactions specified by a genome of evolvable bits. Genome specifications for dynamics that can map specific gene expression patterns in early development onto specific point attractor patterns in later development are essentially impossible to discover by chance mutation alone, even for small networks. We show that selection for approximate mappings, dynamically maintained in the states comprising limit cycles, can accelerate evolution by at least an order of magnitude. These results suggest that self-organizing dynamics that occur within lifetimes can, in principle, guide natural selection across lifetimes.

scholarly journals Beyond the ENCODE project: using genomics and epigenomics strategies to study enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130022 ◽  
Author(s):  
Noboru Jo Sakabe ◽  
Marcelo A. Nobrega
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Dna Interaction ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Genome Wide ◽  
Identify Transcription Factor ◽  
Specific Proteins ◽  
Species Specific

The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis -regulatory elements) in entire genomes. Comparing protein–DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis -regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein–DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression.

scholarly journals Global Analysis of Cell Type-Specific Gene Expression

2003 ◽  
Vol 4 (2) ◽  
pp. 208-215 ◽  
Author(s):  
David W. Galbraith
Keyword(s):  
Gene Expression ◽  
Fluorescent Protein ◽  
Global Analysis ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Global Gene Expression ◽  
Cell Types ◽  
Reasonable Assumption ◽  
Specific Gene ◽  
Different Cell Types

The tissues and organs of multicellular eukaryotes are frequently observed to comprise complex three-dimensional interspersions of different cell types. It is a reasonable assumption that different global patterns of gene expression are found within these different cell types. This review outlines general experimental strategies designed to characterize these global gene expression patterns, based on a combination of methods of transgenic fluorescent protein (FP) expression and targeting, of flow cytometry and sorting and of high-throughput gene expression analysis.

scholarly journals The Potential Role of Genetic Assimilation during Maize Domestication

2017 ◽  
Author(s):  
Anne Lorant ◽  
Sarah Pedersen ◽  
Irene Holst ◽  
Matthew B. Hufford ◽  
Klaus Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zea Mays ◽  
Potential Role ◽  
Expression Patterns ◽  
Genetic Assimilation ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms ◽  
Maize Domestication

ABSTRACTDomestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. Recent research, in which maize and teosinte (i.e., wild maize) were exposed to environments similar to the time of domestication, resulted in a plastic induction of domesticated phenotypes in teosinte and little response to environment in maize. These results suggest that early agriculturalists may have selected for genetic mechanisms that cemented domestication phenotypes initially induced by a plastic response of teosinte to environment, a process known as genetic assimilation. To better understand this phenomenon and the potential role of environment in maize domestication, we examined differential gene expression in maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis) between past and present conditions. We identified a gene set of over 2000 loci showing a change in expression across environmental conditions in teosinte and invariance in maize. In fact, overall we observed both greater plasticity in gene expression and more substantial re-wiring of expression networks in teosinte across environments when compared to maize. While these results suggest genetic assimilation played at least some role in domestication, genes showing expression patterns consistent with assimilation are not significantly enriched for previously identified domestication candidates, indicating assimilation did not have a genome-wide effect.

scholarly journals Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1606
Author(s):  
Shuai Zhang ◽  
Ruixue Wang ◽  
Cheng Huang ◽  
Ludan Zhang ◽  
Lin Sun
Keyword(s):  
Gene Expression ◽  
Sex Chromosome ◽  
Global Gene Expression ◽  
Regulatory Genes ◽  
Dosage Effect ◽  
Macromolecular Complex ◽  
Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Modulation Of Gene Expression

Aneuploidy, which disrupts the genetic balance due to partial genome dosage changes, is usually more detrimental than euploidy variation. To investigate the modulation of gene expression in aneuploidy, we analyzed the transcriptome sequencing data of autosomal and sex chromosome trisomy in Drosophila. The results showed that most genes on the varied chromosome (cis) present dosage compensation, while the remainder of the genome (trans) produce widespread inverse dosage effects. Some altered functions and pathways were identified as the common characteristics of aneuploidy, and several possible regulatory genes were screened for an inverse dosage effect. Furthermore, we demonstrated that dosage changes of inverse regulator Inr-a/pcf11 can produce a genome-wide inverse dosage effect. All these findings suggest that the mechanism of genomic imbalance is related to the changes in the stoichiometric relationships of macromolecular complex members that affect the overall function. These studies may deepen the understanding of gene expression regulatory mechanisms.

scholarly journals Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

2021 ◽  
Vol 17 ◽  
pp. 117693432110413
Author(s):  
Chaoxin Zhang ◽  
Tao Wang ◽  
Tongyan Cui ◽  
Shengwei Liu ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phylogenetic Analysis ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Genome Wide ◽  
A Genome

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPβ, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

scholarly journals Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic

2019 ◽  
Vol 116 (30) ◽  
pp. 14995-15000 ◽  
Author(s):  
Justyna Cholewa-Waclaw ◽  
Ruth Shah ◽  
Shaun Webb ◽  
Kashyap Chhatbar ◽  
Bernard Ramsahoye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rett Syndrome ◽  
Transcription Initiation ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
A Genome ◽  
The Impact

Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here, we integrate quantitative, multidimensional experimental analysis and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose binding to DNA creates “slow sites” in gene bodies. We hypothesize that waves of slowed-down RNA polymerase II formed behind these sites travel backward and indirectly affect initiation, reminiscent of defect-induced shockwaves in nonequilibrium physics transport models. This mechanism differs from conventional gene-regulation mechanisms, which often involve direct modulation of transcription initiation. Our findings point to a genome-wide function of DNA methylation that may account for the reversibility of Rett syndrome in mice. Moreover, our combined theoretical and experimental approach provides a general method for understanding how global gene-expression patterns are choreographed.

The frequency of druggable targets in localized prostate cancer: Initial analysis from the Decipher GRID.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 98-98
Author(s):  
Nicholas Erho ◽  
Mohammed Alshalalfa ◽  
Penelope J. Wood ◽  
Mandeep Takhar ◽  
Hussam Al-Deen Ashab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Relevance ◽  
Expression Patterns ◽  
High Expression ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Resource ◽  
Druggable Targets ◽  
Low Expression

98 Background: Prostate cancers patient management has been enhanced with commercially available genomic prognostic tests such as the Decipher prostate cancer classifier that are useful for making treatment decision-making. In addition to being the most validated predictor of metastasis in prostate cancer, Decipher is also a genome-wide assay that measures the expression of many druggable targets. Methods: Decipher GRID (Genomic Resource Information Database), was queried to assess the expression patterns of 14 genes from 5 biological pathways (Table) in 1,850 patients from previously published Decipher validation studies. The frequency of high (or low) expression of each gene was ascertained using a standard and more conservative thresholds based on the median absolute deviation (MAD) metric. For the standard threshold, genes whose high expression is of clinical relevance, patients with gene expression above the median + 1.48*MAD were annotated as high expression and for genes whose low expression is of clinical relevance, patients with gene expression below the median - 1.48*MAD were annotated as low expression. For the conservative threshold, median +/- 2*1.48*MAD was used. Results: See Table. Conclusions: Since every patient receiving the Decipher test also has a genome-wide expression profile, the Decipher GRID will allow researchers to evaluate on a systematic population-level the expression of genes that may be targeted with existing therapies. Such information may be useful for selection of optimal systemic therapy and inclusion into clinical trials of novel targeted agents. This rich genomic resource is being made available on a research use only basis to prostate cancer researchers and to clinicians seeking to uncover individualized genomic insights for patients to advance precision medicine. [Table: see text]

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