59,467 results match your criteria promoters


GENERALIZED AND TISSUE SPECIFIC GLUCOCORTICOID RESISTANCE.

Mol Cell Endocrinol 2021 Apr 14:111277. Epub 2021 Apr 14.

Department of Internal Medicine - Ribeirao Preto Medical School - University of Sao Paulo, Ribeirao Preto, SP, Brazil. Electronic address:

Glucocorticoids (GCs) are steroid hormones that influence several physiologic functions and are among the most frequently prescribed drugs worldwide. Resistance to GCs has been observed in the context of the familial generalized GC resistance (Chrousos' syndrome) or tissue specific GC resistance in chronic inflammatory states. In this review, we have summarized the major factors that influence individual glucocorticoid sensitivity/resistance. Read More

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A transcriptional regulatory module controls lipid accumulation in soybean.

New Phytol 2021 Apr 17. Epub 2021 Apr 17.

State Key Lab of Plant Genomics, Institute of Genetics and Developmental Biology, INASEED, Chinese Academy of Sciences, Beijing, 100101, China.

Soybean (Glycine max) is one of the most important oilseed crops. However, limited information is known about the regulatory mechanism of oil accumulation in soybean. In this study, a member of tandem CCCH zinc finger (TZF) proteins, GmZF392, from our previous RNA-seq analysis for seed-preferred transcription factors, was found to function as a positive regulator of lipid production. Read More

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Improving the design of an oxidative stress sensing biosensor in yeast.

FEMS Yeast Res 2021 Apr 17. Epub 2021 Apr 17.

Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, M5S 1A1, Canada.

Transcription factor (TF)-based biosensors have proven useful for increasing biomanufacturing yields, large-scale functional screening, and in environmental monitoring. Most yeast TF-based biosensors are built from natural promoters, resulting in large DNA parts retaining considerable homology to the host genome, which can complicate biological engineering efforts. There is a need to explore smaller, synthetic biosensors to expand the options for regulating gene expression in yeast. Read More

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The Murine MHC Class II Super Enhancer Contains a Functionally Redundant CTCF-Binding Component and a Novel Element Critical for Maximal Expression.

J Immunol 2021 Apr 16. Epub 2021 Apr 16.

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA

In both humans and mice, CTCF-binding elements form a series of interacting loops across the MHC class II (MHC-II) locus, and CTCF is required for maximal MHC-II gene expression. In humans, a CTCF-bound chromatin insulator termed and a super enhancer (SE) situated in the intergenic region between and play critical roles in regulating MHC-II expression. In this study, we identify a similar SE, termed located between and of the mouse that contains a CTCF site () and a novel region of high histone H3K27 acetylation. Read More

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Silylium Ions: From Elusive Reactive Intermediates to Potent Catalysts.

Chem Rev 2021 Apr 16. Epub 2021 Apr 16.

Institut für Chemie, Technische Universität Berlin, Strasse des 17 Juni 115, 10623 Berlin, Germany.

The history of silyl cations has all the makings of a drama but with a happy ending. Being considered reactive intermediates impossible to isolate in the condensed phase for decades, their actual characterization in solution and later in solid state did only fuel the discussion about their existence and initially created a lot of controversy. This perception has completely changed today, and silyl cations and their donor-stabilized congeners are now widely accepted compounds with promising use in synthetic chemistry. Read More

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Decoupling transcription factor expression and activity enables dimmer switch gene regulation.

Science 2021 Apr;372(6539):292-295

Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

Gene-regulatory networks achieve complex mappings of inputs to outputs through mechanisms that are poorly understood. We found that in the galactose-responsive pathway in , the decision to activate the transcription of genes encoding pathway components is controlled independently from the expression level, resulting in behavior resembling that of a mechanical dimmer switch. This was not a direct result of chromatin regulation or combinatorial control at galactose-responsive promoters; rather, this behavior was achieved by hierarchical regulation of the expression and activity of a single transcription factor. Read More

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Mechanisms of enhancer action: the known and the unknown.

Genome Biol 2021 Apr 15;22(1):108. Epub 2021 Apr 15.

Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.

Differential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic and phylogenetic diversity of cell types. A key regulator of differential gene expression programs are the enhancers, the gene-distal cis-regulatory sequences that govern spatiotemporal and quantitative expression dynamics of target genes. Enhancers are widely believed to physically contact the target promoters to effect transcriptional activation. Read More

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ChIP-BIT2: a software tool to detect weak binding events using a Bayesian integration approach.

BMC Bioinformatics 2021 Apr 15;22(1):193. Epub 2021 Apr 15.

Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, 900 North Glebe Road, Arlington, VA, 22203, USA.

Background: ChIP-seq combines chromatin immunoprecipitation assays with sequencing and identifies genome-wide binding sites for DNA binding proteins. While many binding sites have strong ChIP-seq 'peak' observations and are well captured, there are still regions bound by proteins weakly, with a relatively low ChIP-seq signal enrichment. These weak binding sites, especially those at promoters and enhancers, are functionally important because they also regulate nearby gene expression. Read More

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DNA methylation and protein expression of Wnt pathway markers in progressive glioblastoma.

Pathol Res Pract 2021 Apr 5;222:153429. Epub 2021 Apr 5.

Department of Laboratory Medicine, University of Pecs, School of Medicine, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary. Electronic address:

Background: Wnt signaling plays important roles in tumorigenesis, invasiveness and therapeutic resistance of glioblastoma (GBM).

Methods: We simultaneously investigated six Wnt pathway markers (Wnt5a, Fzd-2, beta-catenin, Wnt3a, Wnt7b, Fzd-10) at epigenetic and protein levels in 21 sequential formalin-fixed paraffin-embedded GBM pairs and controls.

Results: Expression levels of Wnt5a, beta-catenin and Wnt3a proteins either moderately or significantly increased, while those of Fzd-2, Wnt7b and Fzd-10 decreased in the primary (GBM-P) and recurrent (GBM-R) tumors compared to the controls. Read More

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CpG content-dependent associations between transcription factors and histone modifications.

PLoS One 2021 15;16(4):e0249985. Epub 2021 Apr 15.

Max Planck Institute for Informatics, Computational Biology and Applied Algorithmics, Saarbrücken, Germany.

Understanding the factors that underlie the epigenetic regulation of genes is crucial to understand the gene regulatory machinery as a whole. Several experimental and computational studies examined the relationship between different factors involved. Here we investigate the relationship between transcription factors (TFs) and histone modifications (HMs), based on ChIP-seq data in cell lines. Read More

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Effect of Species Probiotics on Growth Performance of Dual-Purpose Chicken.

Vet Med (Auckl) 2021 6;12:75-83. Epub 2021 Apr 6.

Department of Veterinary Parasitology, Wolaita Sodo University, School of Veterinary Medicine, Wolaita Sodo, Ethiopia.

Introduction: In-feed probiotics are becoming attractive alternatives to antibiotics in the poultry industry due to the ever-growing strict prohibitions on antibiotic growth promoters (AGP) in animal production.

Methods: The study was conducted to investigate the effects of and on the growth performance of 120 day-olds randomly selected Sasso dual-purpose chicken. They were divided into four groups with two replicates per group and 15 chicks per replicate. Read More

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Identification and Regulation of Tomato Serine/Arginine-Rich Proteins Under High Temperatures.

Front Plant Sci 2021 29;12:645689. Epub 2021 Mar 29.

Department of Biosciences, Molecular Cell Biology of Plants, Goethe University, Frankfurt am Main, Germany.

Alternative splicing is an important mechanism for the regulation of gene expression in eukaryotes during development, cell differentiation or stress response. Alterations in the splicing profiles of genes under high temperatures that cause heat stress (HS) can impact the maintenance of cellular homeostasis and thermotolerance. Consequently, information on factors involved in HS-sensitive alternative splicing is required to formulate the principles of HS response. Read More

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Spatial Organization of Chromatin: Transcriptional Control of Adaptive Immune Cell Development.

Front Immunol 2021 29;12:633825. Epub 2021 Mar 29.

Division of Biological Sciences, University of California, San Diego, La Jolla, CA, United States.

Higher-order spatial organization of the genome into chromatin compartments (permissive and repressive), self-associating domains (TADs), and regulatory loops provides structural integrity and offers diverse gene regulatory controls. In particular, chromatin regulatory loops, which bring enhancer and associated transcription factors in close spatial proximity to target gene promoters, play essential roles in regulating gene expression. The establishment and maintenance of such chromatin loops are predominantly mediated involving CTCF and the cohesin machinery. Read More

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Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland.

Nat Commun 2021 04 14;12(1):2239. Epub 2021 Apr 14.

Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, MD, 20892, USA.

Enhancers are transcription factor platforms that synergize with promoters to control gene expression. Here, we investigate enhancers that activate gene expression several hundred-fold exclusively in the lactating mouse mammary gland. Using ChIP-seq for activating histone marks and transcription factors, we identify two candidate enhancers and one super-enhancer in the Csn1s2b locus. Read More

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Epstein-Barr virus lytic replication induces ACE2 expression and enhances SARS CoV-2 pseudotyped virus entry in epithelial cells.

J Virol 2021 Apr 14. Epub 2021 Apr 14.

Division of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84132 USA

Understanding factors that affect the infectivity of SARS CoV-2 is central to combatting COVID-19. The virus surface spike protein of SARS CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We find that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. Read More

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Recruitment of KMT2C/MLL3 to DNA damage sites mediates DNA damage responses and regulates PARP inhibitor sensitivity in cancer.

Cancer Res 2021 Apr 14. Epub 2021 Apr 14.

Department of Cancer Biology, Wake Forest University School of Medicine

When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here we report that KMT2 mutations occur frequently in non-small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Read More

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[Anti-Aging - healthy aging].

Authors:
Thomas Münzer

Dtsch Med Wochenschr 2021 Apr 14;146(8):543-551. Epub 2021 Apr 14.

Anti-aging products still are a big business worldwide. The most active promoters of anti-aging products currently are internet dealers, the cosmetic and the dairy industry or companies that sell nutritional supplements. Only a few of the advertised substances however have been studied in clinical trials under robust conditions. Read More

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The p53/NF-kappaB-dependent induction of sestrin2 by amyloid-beta peptides exerts antioxidative actions in neurons.

Free Radic Biol Med 2021 Apr 11. Epub 2021 Apr 11.

Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei City 112, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei City 112, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei City 112, Taiwan. Electronic address:

Accumulation of senile plaques mainly composed of neurotoxic amyloid-beta peptide (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Sestrin2 inducible by various types of stressors is known to promote autophagy and exert antioxidative effects. In this work, we revealed the molecular mechanisms underlying Aβ induction of sestrin2 and tested whether antioxidation, in addition to autophagy regulation, also contributes to its neuroprotective effects in primary rat cortical neurons. Read More

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Parallel genetics of regulatory sequences using scalable genome editing in vivo.

Cell Rep 2021 Apr;35(2):108988

Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str. 28, 10115 Berlin, Germany. Electronic address:

How regulatory sequences control gene expression is fundamental for explaining phenotypes in health and disease. Regulatory elements must ultimately be understood within their genomic environment and development- or tissue-specific contexts. Because this is technically challenging, few regulatory elements have been characterized in vivo. Read More

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Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing.

Cell Rep 2021 Apr;35(2):108977

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla 41092, Spain; Topology and DNA Breaks Group, Spanish National Cancer Centre (CNIO), Madrid 28029, Spain. Electronic address:

Accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered positive facilitators of transcription. Here, we show that, in contrast to this general assumption, human topoisomerase IIα (TOP2A) activity at promoters represses transcription of immediate early genes such as c-FOS, maintaining them under basal repressed conditions. Read More

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P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Drug Discovery and Design Center, The Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Read More

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Low biological fluctuation of mitochondrial CpG and non-CpG methylation at the single-molecule level.

Sci Rep 2021 Apr 13;11(1):8032. Epub 2021 Apr 13.

Department of Tumor Escape, Resistance and Immunity, TGF-Beta and Immuno-Regulation Team, Cancer Research Centre of Lyon (CRCL), INSERM U 1052, CNRS UMR 5286, UCBL1, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex 08, France.

Mammalian cytosine DNA methylation (5mC) is associated with the integrity of the genome and the transcriptional status of nuclear DNA. Due to technical limitations, it has been less clear if mitochondrial DNA (mtDNA) is methylated and whether 5mC has a regulatory role in this context. Here, we used bisulfite-independent single-molecule sequencing of native human and mouse DNA to study mitochondrial 5mC across different biological conditions. Read More

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Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model.

Sci Rep 2021 Apr 13;11(1):8083. Epub 2021 Apr 13.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia.

While transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Read More

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Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden.

Nat Commun 2021 04 13;12(1):2229. Epub 2021 Apr 13.

Genome Institute of Singapore (GIS), A*STAR, Singapore, Singapore.

Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood. Read More

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Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney.

Nat Commun 2021 04 13;12(1):2190. Epub 2021 Apr 13.

Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.

The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. Read More

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Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication.

Genome Biol 2021 Apr 13;22(1):103. Epub 2021 Apr 13.

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.

Background: Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80-100 million years ago.

Results: We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Read More

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Analysis of Populus glycosyl hydrolase family I members and their potential role in the ABA treatment and drought stress response.

Plant Physiol Biochem 2021 Apr 5;163:178-188. Epub 2021 Apr 5.

State Key Laboratory of Tree Genetics and Breeding, Research Institute of Tropical Forestry, Chinese Academy of Forestry, Guangzhou, Guangdong, 510520, China. Electronic address:

Glycoside hydrolase family 1 (GH1) β-glucosidases (BGLUs) are encoded by a large number of genes and are involved in many developmental processes and stress responses in plants. Due to their importance in plant growth and development, genome-wide analyses have been conducted in the model plant species Arabidopsis thaliana, rice and maize but not in woody plant species, which have important economic and ecological value. In this study, we systematically analyzed Populus BGLUs (PtBGLUs) and demonstrated the involvement of several genes under stress conditions. Read More

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Proteasome subunit beta type-8 from sevenband grouper negatively regulates cytokine responses by interfering NF-κB signaling upon nervous necrosis viral infection.

Fish Shellfish Immunol 2021 Apr 13;113:118-124. Epub 2021 Apr 13.

Department of Aqualife Medicine, Chonnam National University, Yeosu, Republic of Korea. Electronic address:

During viral infection, proper regulation of immune signaling is essential to ensure successful clearance of virus. Immunoproteasome is constitutively expressed and gets induced during viral infection by interferon signaling and contributes to regulate proinflammatory cytokine production and activation of the NF-κB pathway. In this study, we identified Hs-PSMB8, a member of the proteasome β-subunits (PSMB) family, as a negative regulator of NF-κB responses during NNV infection. Read More

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Bcl-xL Dynamics under the Lens of Protein Structure Networks.

J Phys Chem B 2021 Apr 13. Epub 2021 Apr 13.

Computational Biology Laboratory, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Understanding the finely orchestrated interactions leading to or preventing programmed cell death (apoptosis) is of utmost importance in cancer research because the failure of these systems could eventually lead to the onset of the disease. In this regard, the maintenance of a delicate balance between the promoters and inhibitors of mitochondrial apoptosis is crucial, as demonstrated by the interplay among the Bcl-2 family members. In particular, B-cell lymphoma extra-large (Bcl-x) is a target of interest due to the forefront role of its dysfunctions in cancer development. Read More

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Targeting the Vav1/miR‑29b axis as a potential approach for treating selected molecular subtypes of triple‑negative breast cancer.

Oncol Rep 2021 May 13;45(5). Epub 2021 Apr 13.

Department of Translational Medicine, University of Ferrara, I-44121 Ferrara, Italy.

MicroRNA (miR)‑29b has been reported to play a controversial role in breast cancer, particularly triple‑negative breast cancer (TNBC). Based on our previous data revealing that the PU.1‑mediated expression of miR‑29b in cells from acute myeloid leukemia is sustained by Vav1, the potential role of this multidomain protein in modulating miR‑29b levels in breast tumor cells, in which Vav1 is ecstopically expressed and shows a nuclear accumulation, was investigated. Read More

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