scholarly journals Physical association of functionally antagonistic enzymes: KDM5A interacts with MLLs to regulate gene expression in a promoter specific manner facilitating EMT and pluripotency

2021 ◽  
Author(s):  
R Kirtana ◽  
Soumen Manna ◽  
Samir Kumar Patra

AbstractDifferential expression of genes involved in physiological processes are a collaborative outcome of interactions among signalling molecules, downstream effectors and epigenetic modifiers, which together dictate the regulation of genes in response to specific stimuli. MLLs and KDM5A are functionally antagonistic proteins as one acts as writer and the other as eraser of the active chromatin mark, i.e., H3K4me3. KDM5A promotes EMT by occupying promoters of both epithelial and mesenchymal markers. Through this work, it is illustrated that when bound to E-cadherin promoter, KDM5A acts as a classical repressor by demethylating H3K4me3, but on mesenchymal marker promoters, it acts as a transcriptional activator by inhibiting the activity of HDACs and increasing H3K18ac. Further it is demonstrated that KDM5A occupancy enhances either MLL1 or MLL2 by physically interacting with them and that signalling pathways regulate the enzymatic activity of KDM5A probably by phosphorylation. When not active, KDM5A signals for MLL occupancy, a mechanism that can be called epigenetic signalling.

2003 ◽  
Vol 83 (4) ◽  
pp. 1153-1181 ◽  
Author(s):  
HANNAH V. CAREY ◽  
MATTHEW T. ANDREWS ◽  
SANDRA L. MARTIN

Carey, Hannah V., Matthew T. Andrews, and Sandra L. Martin. Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature. Physiol Rev 83: 1153-1181, 2003; 10.1152/physrev. 00008.2003.—Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as −2.9°C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0°C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.


Oncogene ◽  
2021 ◽  
Author(s):  
Panagiotis Papoutsoglou ◽  
Dorival Mendes Rodrigues-Junior ◽  
Anita Morén ◽  
Andrew Bergman ◽  
Fredrik Pontén ◽  
...  

AbstractActivation of the transforming growth factor β (TGFβ) pathway modulates the expression of genes involved in cell growth arrest, motility, and embryogenesis. An expression screen for long noncoding RNAs indicated that TGFβ induced mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) expression in diverse cancer types, thus confirming an earlier demonstration of TGFβ-mediated transcriptional induction of MIR100HG in pancreatic adenocarcinoma. MIR100HG depletion attenuated TGFβ signaling, expression of TGFβ-target genes, and TGFβ-mediated cell cycle arrest. Moreover, MIR100HG silencing inhibited both normal and cancer cell motility and enhanced the cytotoxicity of cytostatic drugs. MIR100HG overexpression had an inverse impact on TGFβ signaling responses. Screening for downstream effectors of MIR100HG identified the ligand TGFβ1. MIR100HG and TGFB1 mRNA formed ribonucleoprotein complexes with the RNA-binding protein HuR, promoting TGFβ1 cytokine secretion. In addition, TGFβ regulated let-7a-2–3p, miR-125b-5p, and miR-125b-1–3p expression, all encoded by MIR100HG intron-3. Certain intron-3 miRNAs may be involved in TGFβ/SMAD-mediated responses (let-7a-2–3p) and others (miR-100, miR-125b) in resistance to cytotoxic drugs mediated by MIR100HG. In support of a model whereby TGFβ induces MIR100HG, which then enhances TGFβ1 secretion, analysis of human carcinomas showed that MIR100HG expression correlated with expression of TGFB1 and its downstream extracellular target TGFBI. Thus, MIR100HG controls the magnitude of TGFβ signaling via TGFβ1 autoinduction and secretion in carcinomas.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Carmen P. Wong ◽  
Urszula T. Iwaniec ◽  
Russell T. Turner

AbstractSixteen-week-old female C57BL/6J mice were sacrificed aboard the International Space Station after 37 days of flight (RR-1 mission) and frozen carcasses returned to Earth. RNA was isolated from interscapular brown adipose tissue (BAT) and gonadal white adipose tissue (WAT). Spaceflight resulted in differential expression of genes in BAT consistent with increased non-shivering thermogenesis and differential expression of genes in WAT consistent with increased glucose uptake and metabolism, adipogenesis, and β-oxidation.


2013 ◽  
Vol 49 (7) ◽  
pp. 707-716 ◽  
Author(s):  
N. Yu. Oparina ◽  
A. V. Snezhkina ◽  
A. F. Sadritdinova ◽  
V. A. Veselovskii ◽  
A. A. Dmitriev ◽  
...  

2020 ◽  
Author(s):  
Andras Bittner ◽  
Jörn van Buer ◽  
Margarete Baier

Abstract Background: The majority of stress-sensitive genes responds to cold and high light in the same direction, if plants face the stresses for the first time. As shown recently for a small selection of genes of the core environmental stress response cluster, pre-treatment of Arabidopsis thaliana with a 24 h long 4 °C cold stimulus modifies cold regulation of gene expression for up to a week at 20 °C, although the primary cold effects are reverted within the first 24 h. Such memory-based regulation is called priming. Here, we analyse the effect of 24 h cold priming on cold regulation of gene expression on a transcriptome-wide scale and investigate if and how cold priming affects light regulation of gene expression.Results: Cold-priming affected cold and excess light regulation of a small subset of genes. In contrast to the strong gene co-regulation observed upon cold and light stress in not-primed plants, most priming-sensitive genes were regulated in a stressor-specific manner in cold-primed plant. Furthermore, almost as much genes were inversely regulated as co-regulated by a 24 h long 4 °C cold treatment and exposure to heat-filtered high light (800 µmol quanta m-2 s-1). Gene ontology enrichment analysis revealed that cold priming preferentially supports expression of genes involved in the defence against plant pathogens upon cold triggering. The regulation took place on the cost of the expression of genes involved in growth regulation and transport. On the contrary, cold priming resulted in stronger expression of genes regulating metabolism and development and weaker expression of defence genes in response to high light triggering. qPCR with independently cultivated and treated replicates confirmed the trends observed in the RNASeq guide experiment.Conclusion: A 24 h long priming cold stimulus activates a several days lasting stress memory that controls cold and light regulation of gene expression and adjusts growth and defence regulation in a stressor-specific manner.


2021 ◽  
Vol 9 ◽  
Author(s):  
Edimar A. Moreira ◽  
Gabriela F. Persinoti ◽  
Letícia R. Menezes ◽  
Douglas A. A. Paixão ◽  
Thabata M. Alvarez ◽  
...  

Lignocellulose digestion in termites is achieved through the functional synergy between gut symbionts and host enzymes. However, some species have evolved additional associations with nest microorganisms that collaborate in the decomposition of plant biomass. In a previous study, we determined that plant material packed with feces inside the nests of Cornitermes cumulans (Syntermitinae) harbors a distinct microbial assemblage. These food nodules also showed a high hemicellulolytic activity, possibly acting as an external place for complementary lignocellulose digestion. In this study, we used a combination of ITS sequence analysis, metagenomics, and metatranscriptomics to investigate the presence and differential expression of genes coding for carbohydrate-active enzymes (CAZy) in the food nodules and the gut of workers and soldiers. Our results confirm that food nodules express a distinct set of CAZy genes suggesting that stored plant material is initially decomposed by enzymes that target the lignin and complex polysaccharides from fungi and bacteria before the passage through the gut, where it is further targeted by a complementary set of cellulases, xylanases, and esterases produced by the gut microbiota and the termite host. We also showed that the expression of CAZy transcripts associated to endoglucanases and xylanases was higher in the gut of termites than in the food nodules. An additional finding in this study was the presence of fungi in the termite gut that expressed CAZy genes. This study highlights the importance of externalization of digestion by nest microbes and provides new evidence of complementary digestion in the context of higher termite evolution.


2000 ◽  
Vol 106 (3) ◽  
pp. 639
Author(s):  
Joshua A. Greenwald ◽  
Babak J. Mehrara ◽  
Jason A. Spector ◽  
Peter J. Fagenholz ◽  
Pierre B. Saadeh ◽  
...  

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