The Naturally Occurring ∆40p53 Isoform Inhibits eRNA Transcription and Enables Context-Specific Regulation During p53 Activation

2020 ◽  
Author(s):  
Cecilia Blair Levandowski ◽  
T. Jones ◽  
Margaret Gruca ◽  
Sivapriya Ramamoorthy ◽  
Robin Dowell ◽  
...  
Keyword(s):  
Naturally Occurring ◽  
P53 Activation ◽  
Specific Regulation ◽  
Context Specific

Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

2021 ◽  
Vol 118 (41) ◽  
pp. e2104832118
Author(s):  
Vinod K. Mony ◽  
Anna Drangowska-Way ◽  
Reka Albert ◽  
Emma Harrison ◽  
Abbas Ghaddar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Gene ◽  
Specific Nature ◽  
C Elegans ◽  
Functional Interactions ◽  
Genetic Epistasis ◽  
Specific Regulation ◽  
Context Specific ◽  
Factor Interactions ◽  
Multicellular Organisms

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”

scholarly journals Context-Specific Regulation of NF-κB Target Gene Expression by EZH2 in Breast Cancers

2011 ◽  
Vol 43 (5) ◽  
pp. 798-810 ◽  
Author(s):  
Shuet Theng Lee ◽  
Zhimei Li ◽  
Zhenlong Wu ◽  
Meiyee Aau ◽  
Peiyong Guan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Breast Cancers ◽  
Target Gene Expression ◽  
Specific Regulation ◽  
Context Specific

Images of Leadership Development From the Inside Out

2015 ◽  
Vol 17 (3) ◽  
pp. 321-336 ◽  
Author(s):  
Heather Cairns-Lee
Keyword(s):  
Leadership Development ◽  
Future Research ◽  
Leadership Roles ◽  
Implicit Leadership ◽  
Implicit Leadership Theories ◽  
Naturally Occurring ◽  
Novel Approach ◽  
Symbolic Reality ◽  
Personalized Approach ◽  
Context Specific

The Problem With the codification of leadership into frameworks, models, and theories that can be taught, leadership, an art that is essentially subjective, symbolic, and context-specific, is “translated into” an objective, pragmatic, and universal domain. Development can be elusive when approached from this universal perspective if external models distract leaders from exploring their own views and practices of leadership. The Solution This article explores the subjective and symbolic reality of those in leadership roles to discover what leaders can learn about their leadership and its development from awareness of their own mental models. These models are illuminated by an exploration of leaders’ naturally occurring metaphors and implicit leadership theories (ILTs) using clean language to acknowledge experience exactly as described while minimizing external influence or interpretation. The Stakeholders Leadership development practitioners can benefit from the innovative personalized approach to surfacing and exploring leaders’ own metaphors facilitated by clean language, offered in this article. Examples are given of the range of leadership metaphors surfaced with this method. Researchers can appreciate a novel approach to qualitative research interviewing and identify future research in surfacing ILTs through naturally occurring metaphor facilitated by clean language.

scholarly journals Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hussein Al-Mossawi ◽  
Nicole Yager ◽  
Chelsea A. Taylor ◽  
Evelyn Lau ◽  
Sara Danielli ◽  
...  
Keyword(s):  
Disease Susceptibility ◽  
Risk Allele ◽  
Genetic Regulation ◽  
Common Variants ◽  
Healthy Individuals ◽  
Cell Immunity ◽  
Gene Sets ◽  
Key Factor ◽  
Specific Regulation ◽  
Context Specific

Abstract IL-7 is a key factor in T cell immunity and common variants at IL7R, encoding its receptor, are associated with autoimmune disease susceptibility. IL7R mRNA is induced in stimulated monocytes, yet a function for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level in healthy individuals, and find that monocyte surface and soluble IL7R (sIL7R) are markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associate with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. Monocytes produce more sIL7R than CD4 + T cells, and the amount is additionally correlated with the expression of DDX39A, encoding a splicing factor. Synovial fluid-derived monocytes from patients with spondyloarthritis are enriched for IL7R+ cells with a unique transcriptional profile that overlaps with IL-7-induced gene sets. Our data thus suggest a previously unappreciated function for monocytes in IL-7 biology and IL7R-associated diseases.

scholarly journals Context-specific regulation of cancer epigenomes by histone and transcription factor methylation

Oncogene ◽  
2013 ◽  
Vol 33 (10) ◽  
pp. 1207-1217 ◽  
Author(s):  
M Sarris ◽  
K Nikolaou ◽  
I Talianidis
Keyword(s):  
Transcription Factor ◽  
Specific Regulation ◽  
Context Specific

scholarly journals Context-specific regulation of monocyte surface IL7R expression and soluble receptor secretion by a common autoimmune risk allele

2018 ◽  
Author(s):  
Hussein Al-Mossawi ◽  
Nicole Yager ◽  
Chelsea Taylor ◽  
Evelyn Lau ◽  
Sara Danielli ◽  
...  
Keyword(s):  
Genetic Regulation ◽  
Biliary Cirrhosis ◽  
Transcriptional Signature ◽  
Cell Immunity ◽  
Key Factor ◽  
Multiple Cell ◽  
Specific Regulation ◽  
Context Specific ◽  
Genetically Determined

AbstractIL-7 is a key factor in T-cell immunity and IL7R polymorphisms are implicated in autoimmune pathogenesis. IL7R mRNA is induced in stimulated monocytes in a genetically determined manner, yet a role for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level across multiple cell subsets and conditions in healthy individuals. We find monocyte surface and soluble IL7R (sIL7R) protein are markedly expressed in response to lipopolysaccharide (LPS). We further demonstrate alleles of rs6897932, a non-synonymous IL7R polymorphism associated with susceptibility to Multiple Sclerosis, Ankylosing Spondylitis and Primary Biliary Cirrhosis, form the key determinant of both surface IL7R and sIL7R in the context of inflammation. No effect of this allele was observed in unstimulated monocytes or across lymphoid subsets. Production of sIL7R by monocytes greatly exceeded that of CD4+ T-cells, and was strongly associated with both rs6897932 genotype and expression of the splicing factor gene DDX39A. Stimulated monocytes were sensitive to exogenous IL-7, which elicits a defined transcriptional signature. Flow cytometry and single-cell sequencing of synovial fluid derived monocytes from patients with spondyloarthritis showed an enlarged subset of IL7R+ monocytes with a unique transcriptional profile that markedly overlaps that induced by IL-7 in-vitro and shows similarity to the previously described ‘Mono4’ subset. These data demonstrate disease-associated genetic variants at IL7R specifically impact monocyte surface IL7R and sIL7R following innate immune stimulation, suggesting a previously unappreciated key role for monocytes in IL-7 pathway biology and IL7R-associated diseases.

scholarly journals Alcohol causes lasting differential transcription in Drosophila mushroom body neurons

2019 ◽  
Author(s):  
Emily Petruccelli ◽  
Nicolas Ledru ◽  
Karla R. Kaun
Keyword(s):  
Mushroom Body ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Types ◽  
Memory Encoding ◽  
Sensory Cues ◽  
New Methods ◽  
Specific Regulation ◽  
Context Specific ◽  
Differential Transcription

AbstractRepeated alcohol experiences can produce long-lasting memories for sensory cues associated with intoxication. These memories can ultimately trigger relapse in individuals recovering from alcohol use disorder (AUD). The molecular mechanisms by which alcohol changes memories to become long-lasting and inflexible remain unclear. New methods to analyze gene expression within precise neuronal cell-types can provide further insight towards AUD prevention and treatment. Here, we employed genetic tools in Drosophila melanogaster to investigate the lasting consequences of ethanol on transcription in memory-encoding neurons. Drosophila rely on mushroom body (MB) neurons to make associative memories, including memories of ethanol-associated sensory cues. Differential expression analyses found that distinct transcripts, but not genes, in the MB were associated with experiencing ethanol alone compared to forming a memory of an odor cue associated with ethanol. These findings reveal the dynamic and highly context-specific regulation of splicing associated with encoding behavioral experiences. Our data thus demonstrate that alcohol can have lasting effects on transcription and RNA processing during memory formation, and identify new transcript targets for future AUD and addiction investigation.

scholarly journals UniPath: A uniform approach for pathway and gene-set based analysis of heterogeneity in single-cell epigenome and transcriptome profiles

2019 ◽  
Author(s):  
Smriti Chawla ◽  
Sudhagar Samydurai ◽  
Say Li Kong ◽  
Zhenxun Wang ◽  
Wai Leong Tam ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Single Cells ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Mouse Cell ◽  
Open Chromatin ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Specific Regulation ◽  
Context Specific

AbstractHere, we introduce UniPath, for representing single-cells using pathway and gene-set enrichment scores by a transformation of their open-chromatin or gene-expression profiles. Besides being robust to variability in dropout, UniPath provides consistency and scalability in estimating gene-set enrichment scores for every cell. UniPath’s approach of predicting temporal-order of single-cells using their gene-set activity score enables suppression of known covariates. UniPath based analysis of mouse cell atlas yielded surprising, albeit biologically-meaningful co-clustering of cell-types from distant organs and helped in annotating many unlabeled cells. By enabling unconventional analysis, UniPath also proves to be useful in inferring context-specific regulation in cancer cells.

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