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49 publications found.

The aryl hydrocarbon receptor cell intrinsically promotes resident memoryCD8 T cell differentiation and function.
Published: January, 2023

Abstract: The Aryl hydrocarbon receptor (Ahr) regulates the differentiation and function of CD4 T cells; however, its cell-intrinsic role in CD8 T cells remains elusive. Herein we show that Ahr acts as a promoter of resident memory CD8 T cell...
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TCDD induces multigenerational alterations in the expression ofmicroRNA in the thymus through epigenetic modifications
Published: December, 2022

Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of miRNAs (miRs)...
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FXR inhibition may protect from SARS-CoV-2 infection by reducingACE2.
Published: December, 2022

Abstract: Prevention of SARS-CoV-2 infection through the modulation of viral host receptors, such as ACE2, could represent a new chemoprophylactic approach for COVID-19 complementing vaccination. However, the mechanisms controlling ACE2 expression remain el...
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Intranasal administration of Acinetobacter lwoffii in a murine model ofasthma induces IL-6-mediated protection associated with cecal microbiotachanges.
Published: December, 2022

Abstract: BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the i...
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Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes
Published: May, 2022

Abstract: Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used...
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Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in zebrafish embryos
Published: January, 2022

Abstract: DNA accessibility of cis-regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many genes regulating embryonic development have been identified, the underlying CRE dynamics controlli...
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Autocrine Vitamin D-signaling switches off pro-inflammatory programsof Th1 cells
Published: October, 2021

Abstract: The molecular mechanisms governing orderly shutdown and retraction of CD4+ T helper (Th)1 responses remain poorly understood. Here, we show that complement triggers contraction of Th1 responses by inducing intrinsic expression of the vitamin D (Vi...
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Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells.
Published: August, 2021

Abstract: A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing i...
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Inactivating histone deacetylase HDA promotes longevity by mobilizingtrehalose metabolism.
Published: March, 2021

Abstract: Histone acetylations are important epigenetic markers for transcriptional activation in response to metabolic changes and various stresses. Using the high-throughput SEquencing-Based Yeast replicative Lifespan screen method and the yeast knockout ...
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Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.
Published: December, 2020

Abstract: Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-...
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Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.
Published: November, 2020

Abstract: Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involve...
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Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.
Published: November, 2020

Abstract: BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling ...
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Age-associated cryptic transcription in mammalian stem cells is linked topermissive chromatin at cryptic promoters
Published: October, 2020

Abstract: Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. I...
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Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.
Published: May, 2020

Abstract: Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B...
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Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown/Beige Adipocytes
Published: February, 2020

Abstract: Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi-omics data, transferrin...
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Wnt5a is a transcriptional target of Gli3 and Trps1 at the onset of chondrocyte hypertrophy.
Published: September, 2019

Abstract: During endochondral ossification, the differentiation of proliferating into hypertrophic chondrocytes is a key step determining the pace of bone formation and the future length of the skeletal elements. A variety of transcription factors are expre...
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Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells.
Published: August, 2019

Abstract: Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripot...
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Development and epigenetic plasticity of murine Müller glia.
Published: July, 2019

Abstract: The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progen...
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Whsc1 links pluripotency exit with mesendoderm specification.
Published: July, 2019

Abstract: How pluripotent stem cells differentiate into the main germ layers is a key question of developmental biology. Here, we show that the chromatin-related factor Whsc1 (also known as Nsd2 and MMSET) has a dual role in pluripotency exit and germ layer...
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The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.
Published: March, 2019

Abstract: The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify po...
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EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation.
Published: February, 2019

Abstract: Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Usin...
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Spatial confinement downsizes the inflammatory response of macrophages.
Published: December, 2018

Abstract: Macrophages respond to chemical/metabolic and physical stimuli, but their effects cannot be readily decoupled in vivo during pro-inflammatory activation. Here, we show that preventing macrophage spreading by spatial confinement, as imposed by micr...
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Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability.
Published: August, 2018

Abstract: Histone H3 lysine 9 methylation (H3K9me) mediates heterochromatic gene silencing and is important for genome stability and the regulation of gene expression. The establishment and epigenetic maintenance of heterochromatin involve the recruitment o...
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An Integrated and Semiautomated Microscaled Approach to Profile Cis-Regulatory Elements by Histone Modification ChIP-Seq for Large-Scale Epigenetic Studies.
Published: June, 2018

Abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) is the preferred approach to map histone modifications and identify cis-regulatory DNA elements throughout the genome. Multiple methods have been described to increase the efficiency ...
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Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation.
Published: June, 2018

Abstract: Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recogniz...
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Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.
Published: May, 2018

Abstract: The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix. Although Notch and other signalling pathways have...
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Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.
Published: May, 2018

Abstract: Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic β cells, between the insulin ( ...
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A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.
Published: May, 2018

Abstract: Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown ...
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Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis.
Published: May, 2018

Abstract: Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling g...
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Contrasting epigenetic states of heterochromatin in the different types of mouse pluripotent stem cells.
Published: April, 2018

Abstract: Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent naive and primed pluripotency states, respectively, and are maintained in vitro by specific signalling pathways. Furthermore, ESCs cultured in serum-free medium with two ...
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Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Published: March, 2018

Abstract: Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible...
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Functional dissection of Drosophila melanogaster SUUR protein influence on H3K27me3 profile
Published: December, 2017

Abstract: Background In eukaryotes, heterochromatin replicates late in S phase of the cell cycle and contains specific covalent modifications of histones. SuUR mutation found in Drosophila makes heterochromatin replicate earlier than in wild type and red...
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The RPMI-1640 vitamin mixture promotes bovine blastocyst development in vitro and downregulates gene expression of TXNIP with epigenetic modification of associated histones
Published: August, 2017

Abstract: Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short- and long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker for prei...
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Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression
Published: April, 2017

Abstract: BACKGROUND: H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression. METHODS: We investigated genome-wide H3K27me3 histone methy...
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Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.
Published: February, 2017

Abstract: Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, inc...
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Differentiation of Mouse Enteric Nervous System Progenitor Cells is Controlled by Endothelin 3 and Requires Regulation of Ednrb by SOX10 and ZEB2
Published: January, 2017

Abstract: Background & Aims Maintenance and differentiation of progenitor cells in the developing enteric nervous system (ENS) are controlled by molecules such as the signaling protein endothelin 3 (EDN3), its receptor (the endothelin receptor type B...
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In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development
Published: October, 2016

Abstract: Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pa...
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Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells
Published: August, 2016

Abstract: It has recently been appreciated that NK cells exhibit many features reminiscent of adaptive immune cells. Considerable heterogeneity exists with respect to the ligand specificity of individual NK cells and as such, a subset of NK cells can respon...
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Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis
Published: July, 2016

Abstract: Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contribute synergist...
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Rebalancing gene haploinsufficiency in vivo by targeting chromatin
Published: June, 2016

Abstract: Congenital heart disease (CHD) affects eight out of 1,000 live births and is a major social and health-care burden. A common genetic cause of CHD is the 22q11.2 deletion, which is the basis of the homonymous deletion syndrome (22q11.2DS), also kno...
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Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain
Published: May, 2016

Abstract: Chronic pain is a common and devastating condition that induces well-characterized changes in neurons and microglia. One major unanswered question is why these changes should persist long after the precipitating injury has healed. Here, we suggest...
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KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.
Published: May, 2016

Abstract: The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expre...
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Desensitization and incomplete recovery of hepatic target genes after chronic thyroid hormone treatment and withdrawal in male adult mice
Published: February, 2016

Abstract: Here, we examined changes in hepatic gene expression and serum TH/thyrotropin (TSH) levels in adult male mice treated either with a single T3 (20 g/100 g body weight) injection (acute T3) or daily injections for 14 days (chronic T3) followed ...
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Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors
Published: January, 2016

Abstract: Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) as...
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Methionine-dependent histone methylation at developmentally important gene loci in mouse preimplantation embryos
Published: December, 2015

Abstract: The involvement of specific nutrients in epigenetic gene regulation is a possible mechanism underlying nutrition-directed phenotypic alteration. However, the involvement of nutrients in gene-specific epigenetic regulation remains poorly understood...
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Dynamic changes in histone modifications precede de novo DNA methylation in oocytes
Published: December, 2015

Abstract: Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a nu...
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Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells
Published: December, 2014

Abstract: The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex viv...
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Concomitant downregulation of the imprinted genes DLK1 and MEG3 at 14q32.2 by epigenetic mechanisms in urothelial carcinoma
Published: November, 2014

Abstract: Background The two oppositely imprinted and expressed genes, DLK1 and MEG3, are located in the same gene cluster at 14q32. Previous studies in bladder cancer have suggested that tumor suppressor genes are located in this region, but these have no...
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GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development.
Published: April, 2014

Abstract: The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underly...
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