Epigenetic Remodeling of Delta FosB Protein: Its Role in Regulation of Stress

AbstractMetabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.

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Abstract 61: Transient "rest" reinvigorates exhausted CAR T cells via epigenetic remodeling

10.1158/1538-7445.am2021-61 ◽

2021 ◽

Author(s):

Evan W. Weber ◽

Crystal Mackall

Keyword(s):

T Cells ◽

Car T Cells ◽

Car T ◽

Epigenetic Remodeling

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NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink

Nature Chemical Biology ◽

10.1038/nchembio.1204 ◽

2013 ◽

Vol 9 (5) ◽

pp. 300-306 ◽

Cited By ~ 173

Author(s):

Olesya A Ulanovskaya ◽

Andrea M Zuhl ◽

Benjamin F Cravatt

Keyword(s):

Epigenetic Remodeling

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Establishing a role for environmental toxicant exposure induced epigenetic remodeling in malignant transformation

Seminars in Cancer Biology ◽

10.1016/j.semcancer.2018.11.002 ◽

2019 ◽

Vol 57 ◽

pp. 86-94 ◽

Cited By ~ 4

Author(s):

Kristen M. Humphrey ◽

Sumali Pandey ◽

Jeffery Martin ◽

Tamara Hagoel ◽

Anne Grand’Maison ◽

...

Keyword(s):

Malignant Transformation ◽

Environmental Toxicant ◽

Toxicant Exposure ◽

Epigenetic Remodeling

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The MUC5B-associated variant, rs35705950, resides within an enhancer subject to lineage- and disease-dependent epigenetic remodeling

JCI Insight ◽

10.1172/jci.insight.144294 ◽

2020 ◽

Author(s):

Fabienne Gally ◽

Sarah K. Sasse ◽

Jonathan Kurche ◽

Margaret A. Gruca ◽

Jonathan H. Cardwell ◽

...

Keyword(s):

Epigenetic Remodeling

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The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos

Cellular Physiology and Biochemistry ◽

10.1159/000464389 ◽

2017 ◽

Vol 41 (3) ◽

pp. 1255-1266 ◽

Cited By ~ 11

Author(s):

Jun-Xue Jin ◽

Sanghoon Lee ◽

Anukul Taweechaipaisankul ◽

Geon A. Kim ◽

Byeong Chun Lee

Keyword(s):

Dna Methylation ◽

Formation Rate ◽

Nuclear Reprogramming ◽

In Vitro Development ◽

Histone 3 ◽

Expression Of Genes ◽

Epigenetic Remodeling ◽

Low Efficiency ◽

Vitro Development

Background/Aims: Hypoacetylation caused by aberrant epigenetic nuclear reprogramming results in low efficiency of mammalian somatic cell nuclear transfer (SCNT). Many epigenetic remodeling drugs have been used in attempts to improve in vitro development of porcine SCNT embryos. In this study, we examined the effects of LAQ824, a structurally novel histone acetylase inhibitor, on the nuclear reprogramming and in vitro development of porcine SCNT embryos. Methods: LAQ824 treatment was supplemented during the culture of SCNT embryos. The reprogramming levels were measured by immunofluorescence and quantified by image J software. Relative expression levels of 18 genes were analyzed by quantitative real-time PCR. Results: 100 nM LAQ824 treatment of post-activation SCNT embryos for 24 h significantly improved the subsequent blastocyst formation rate. The LAQ824 treatment enhanced histone 3 lysine 9 (H3K9) levels, histone 4 lysine 12 (H4K12) levels, and reduced global DNA methylation levels as well as anti-5-methylcytosine (5-mC) at the pseudo-pronuclear and 2-cell stages. Furthermore, LAQ824 treatment positively regulated the mRNA expression of genes for histone acetylation (HAT1, HDAC1, 2, 3, and 6), DNA methylation (DNMT1, 3a and 3b), development (Pou5f1, Nanog, Sox2, and GLUT1) and apoptosis (Bax, Bcl2, Caspase 3 and Bak) in blastocysts. Conclusion: Optimum exposure (100 nM for 24 h) to LAQ824 post-activation improved the in vitro development of porcine SCNT embryos by enhancing levels of H3K9 and H4K12, reducing 5-mC, and regulating gene expression.

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Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus Accumbens Preventing Amphetamine Relapse.

10.21203/rs.3.rs-1247241/v1 ◽

2022 ◽

Author(s):

Domênika Rubert Rossato ◽

Higor Zuchetto Rosa ◽

Jéssica Leandra Oliveira Rosa ◽

Laura Hautrive Milanesi ◽

Vinícia Garzella Metz ◽

...

Keyword(s):

Nucleus Accumbens ◽

Tactile Stimulation ◽

Male Rats ◽

Adult Rats ◽

Delta Fosb ◽

The Central Nervous System ◽

Molecular Assessment ◽

Drug Abstinence ◽

The Brain ◽

Abstinence Period

Abstract Amphetamine (AMPH) is a psychostimulant drug frequently related to addiction, which is characterized by functional and molecular changes in the brain reward system, favoring relapse development and pharmacotherapies have shown low effectiveness. Considering the beneficial influences of tactile stimulation (TS) in different diseases that affect the central nervous system (CNS), here we evaluated if TS applied in adult rats could prevent or minimize the AMPH-relapse behavior also accessing molecular neuroadaptations in the Nucleus accumbens (NAc). Following AMPH conditioning in the conditioned place preference (CPP) paradigm, male rats were submitted to TS (15-min session, 3 times a day, for 8 days) during the drug abstinence period, which were re-exposed to the drug in the CPP paradigm for additional 3 days for relapse observation and molecular assessment. Our findings showed that besides AMPH relapse; TS prevented the dopamine transporter (DAT), dopamine 1 receptor (D1R), tyrosine hydroxylase (TH), mu opioid receptor (MOR) increase and AMPH-induced delta FosB (ΔFosB). Based on these outcomes, we propose TS as a useful tool to treat psychostimulant addiction, which subsequent to clinical studies; it could be included in detoxification programs together with pharmacotherapies and psychological treatments already conventionally established.

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Implications of HBV-Driven Epigenetic Remodeling and Its Targets in Liver Cancer Stem Cells

10.21203/rs.3.rs-45377/v1 ◽

2020 ◽

Author(s):

Ayse Banu Demir ◽

Domenico Benvenuto ◽

Bilge Karacicek ◽

Yasemin Erac ◽

Silvia Angeletti ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Liver Cancer ◽

Phylogenetic Analyses ◽

Gene Expression Pattern ◽

Cancer Prognosis ◽

Dependent Manner ◽

Hbv Genotype ◽

Liver Cancer Stem Cells ◽

Epigenetic Remodeling

Abstract Background: Elevated levels of STIM1, an endoplasmic reticulum Ca2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis where microRNAs are also known to be involved. We investigated a possible viral origin of specific microRNAs identified in Huh-7 human liver cancer stem cells with enhanced STIM1 expression. Methods: Computational strategies including phylogenetic analyses were performed on miRNome data obtained from Huh-7 liver cancer stem cells with enhanced STIM1 and/or Orai1 expression originally cultured in the present study. Results: Results revealed two putative regions in HBV genome based on apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions revealed critical human genes of which their transcripts are among the predicted targets of miR3653 which was increased significantly by STIM1 enhancement. Conclusion: This study presents a phylogenetic evidence for an HBV-driven epigenetic remodeling to alter gene expression pattern associated with Ca2+ homeostasis in STIM1-overexpressing liver cancer stem cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the HBV genotype would have a clinical impact on prognosis.

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Abstract MP105: Python Post-prandial Cardiac Adaptation is Supported by Enhanced Metabolism, Reduced Sarcomere Passive Tension, and Epigenetic Remodeling

Circulation Research ◽

10.1161/res.127.suppl_1.mp105 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Claudia Crocini ◽

Kc Woulfe ◽

Cierra J Walker ◽

Christopher D Ozeroff ◽

leslie A leinwand

Keyword(s):

Metabolic Response ◽

Heart Diseases ◽

Chromatin Condensation ◽

Chromatin Accessibility ◽

Passive Tension ◽

Tissue Stiffness ◽

Atp Production ◽

Python Regius ◽

Cardiac Adaptation ◽

Epigenetic Remodeling

Pythons are infrequent feeders that can ingest meals equal to their own body mass. The extreme metabolic response required to digest such large meals is associated with a dramatic increase in the mass of most organs, including the heart. Recently, we have been able to assess functional effects of feeding using isolated python cardiomyocytes and myofibrils, advancing our understanding of extreme cardiac adaptation in python ( Python regius ). Twenty-four hours after feeding, python cardiomyocytes showed prolonged Ca 2+ transients, increased maximal tension and Ca 2+ sensitivity of myofibrils as compared to fasted pythons. Post-prandial positive inotropy was accompanied by enhanced metabolic output via increased mitochondrial ATP production rate and by AMP-dependent kinase (AMPK) activation and phosphofructokinase-2 reduction, suggesting a key role for fatty acid, but not glucose, metabolism after feeding. In addition, 24h post-fed hearts had significantly reduced tissue stiffness and myofibril passive tension. Finally, chromatin condensation was reduced about 30% after feeding in python cardiomyocytes and confirmed by increased histone acetylation, indicating a predominant role for epigenetics in post-prandial adaptation. These results suggest that feeding promotes positive cardiac inotropy in python via a number of coordinated mechanisms to enhance energy production, increase myofibril and tissue compliance, and increase chromatin accessibility. As heart failure is commonly characterized by depressed contractility, compromised energetics, and increased tissue stiffness, assessing post-prandial adaptation in python hearts provides us with powerful insights that could inform the development of therapeutics for human heart diseases.

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