284 results match your criteria cryptic promoters

Integrative RNA-Seq and H3 Trimethylation ChIP-Seq Analysis of Human Lung Cancer Cells Isolated by Laser-Microdissection.

Cancers (Basel) 2021 Apr 5;13(7). Epub 2021 Apr 5.

Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Our previous integrative study in gastric cancer discovered cryptic promoter activation events that drive the expression of important developmental genes. However, it was unclear if such cancer-associated epigenetic changes occurred in cancer cells or other cell types in bulk tissue samples. An integrative analysis consisting of RNA-Seq and H3K4me3 ChIP-Seq was used. Read More

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Cryptic prokaryotic promoters explain instability of recombinant neuronal sodium channels in bacteria.

J Biol Chem 2021 Jan 15:100298. Epub 2021 Jan 15.

Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL USA. Electronic address:

Mutations in genes encoding the human brain-expressed voltage-gated sodium (Na) channels Na1.1, Na1.2, and Na1. Read More

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January 2021

Facile method of curing toxicity in large viral genomes by high-throughput identification and removal of cryptic promoters.

J Virol Methods 2021 01 15;287:113993. Epub 2020 Oct 15.

Department of Biology, York University, Toronto, Canada. Electronic address:

Infectious plant virus clones are challenging to construct and manipulate due to the presence of cryptic promoter sequences that induce toxicity in bacteria. Common methods to overcome toxicity include intron insertion to interrupt toxic open reading frames and the use of Rhizobium or yeast species that do not recognize the same cryptic promoters. Unfortunately, intron insertion must be attempted on a trial and error basis within full-length clones and may change the infection characteristics of the virus. Read More

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January 2021

HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression.

Nucleic Acids Res 2020 11;48(19):10890-10908

Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.

Although endogenous retroviruses (ERVs) are known to harbor cis-regulatory elements, their role in modulating cellular immune responses remains poorly understood. Using an RNA-seq approach, we show that several members of the ERV9 lineage, particularly LTR12C elements, are activated upon HIV-1 infection of primary CD4+ T cells. Intriguingly, HIV-1-induced ERVs harboring transcription start sites are primarily found in the vicinity of immunity genes. Read More

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November 2020

Genetic circuit characterization by inferring RNA polymerase movement and ribosome usage.

Nat Commun 2020 10 5;11(1):5001. Epub 2020 Oct 5.

Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

To perform their computational function, genetic circuits change states through a symphony of genetic parts that turn regulator expression on and off. Debugging is frustrated by an inability to characterize parts in the context of the circuit and identify the origins of failures. Here, we take snapshots of a large genetic circuit in different states: RNA-seq is used to visualize circuit function as a changing pattern of RNA polymerase (RNAP) flux along the DNA. Read More

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October 2020

Histone chaperone FACT represses retrotransposon MERVL and MERVL-derived cryptic promoters.

Nucleic Acids Res 2020 10;48(18):10211-10225

State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, People's Republic of China.

Endogenous retroviruses (ERVs) were usually silenced by various histone modifications on histone H3 variants and respective histone chaperones in embryonic stem cells (ESCs). However, it is still unknown whether chaperones of other histones could repress ERVs. Here, we show that H2A/H2B histone chaperone FACT plays a critical role in silencing ERVs and ERV-derived cryptic promoters in ESCs. Read More

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October 2020

Primary Role of the Nucleosome.

Mol Cell 2020 08;79(3):371-375

Department of Structural Biology, Stanford School of Medicine, Stanford, CA 94305, USA. Electronic address:

Whereas the core nucleosome is thought to serve as a packaging device for the coiling and contraction in length of genomic DNA, we suggest that it serves primarily in the regulation of transcription. A nucleosome on a promoter prevents the initiation of transcription. The association of nucleosomes with most genomic DNA prevents initiation from cryptic promoters. Read More

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Optimisation of Tet-On inducible systems for Sleeping Beauty-based chimeric antigen receptor (CAR) applications.

Sci Rep 2020 08 4;10(1):13125. Epub 2020 Aug 4.

Department of Microbiology and Immunology, University of Otago, Dunedin, Otago, 9010, New Zealand.

Regulated expression of genetic elements that either encode polypeptides or various types of functional RNA is a fundamental goal for gene therapy. Inducible expression may be preferred over constitutive promoters to allow clinician-based control of gene expression. Existing Tet-On systems represent one of the tightest rheostats for control of gene expression in mammals. Read More

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Identification of the Biosynthetic Gene Cluster for the anti-MRSA Lysocins through Gene Cluster Activation Using Strong Promoters of Housekeeping Genes and Production of New Analogs in sp. 3655.

ACS Synth Biol 2020 08 16;9(8):1989-1997. Epub 2020 Jul 16.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States.

The Gram-negative gliding bacteria represent a new and rich source for bioactive natural products. In an effort to discover new antibiotics, we found a cryptic biosynthetic gene cluster (BGC) in sp. 3655 that shared a high similarity with the putative lysocin BGC identified previously from sp. Read More

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Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity.

Nat Commun 2020 06 19;11(1):3153. Epub 2020 Jun 19.

University of Strasbourg, Strasbourg, France.

Mouse embryos acquire global DNA methylation of their genome during implantation. However the exact roles of DNA methyltransferases (DNMTs) in embryos have not been studied comprehensively. Here we systematically analyze the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos. Read More

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A non-canonical promoter element drives spurious transcription of horizontally acquired bacterial genes.

Nucleic Acids Res 2020 05;48(9):4891-4901

Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

RNA polymerases initiate transcription at DNA sequences called promoters. In bacteria, the best conserved promoter feature is the AT-rich -10 element; a sequence essential for DNA unwinding. Further elements, and gene regulatory proteins, are needed to recruit RNA polymerase to the -10 sequence. Read More

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Deciphering the Rules Underlying Xenogeneic Silencing and Counter-Silencing of Lsr2-like Proteins Using CgpS of Corynebacterium glutamicum as a Model.

mBio 2020 02 4;11(1). Epub 2020 Feb 4.

Institut für Bio- und Geowissenschaften, IBG-1: Biotechnologie, Forschungszentrum Jülich, Jülich, Germany

Lsr2-like nucleoid-associated proteins play an important role as xenogeneic silencers (XS) of horizontally acquired genomic regions in actinobacteria. In this study, we systematically analyzed the constraints underlying silencing and counter-silencing of the Lsr2-like protein CgpS in Genome-wide analysis revealed binding of CgpS to regions featuring a distinct drop in GC profile close to the transcription start site (TSS) but also identified an overrepresented motif with multiple A/T steps at the nucleation site of the nucleoprotein complex. Binding of specific transcription factors (TFs) may oppose XS activity, leading to counter-silencing. Read More

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February 2020

Promoter Screening Facilitates Heterologous Production of Complex Secondary Metabolites in Burkholderiales Strains.

ACS Synth Biol 2020 02 7;9(2):457-460. Epub 2020 Feb 7.

Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology , Shandong University , Qingdao , Shandong 266237 , PR China.

Burkholderiales are an emerging source of bioactive secondary metabolites and have the potential to be a robust chassis for metabolites from Gram-negative bacteria. However, only a few constitutive promoters can be utilized in Burkholderiales. Herein, we described the screening of strong constitutive promoters from Burkholderiales strain DSM 7029, and 37 promoters identified from transcriptome sequencing were cloned and characterized using a firefly luciferase reporter and were further verified by qPCR analysis. Read More

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February 2020

A New Way to Discover IRESs in Pathology or Stress Conditions? Harnessing Latest High-Throughput Technologies.

Bioessays 2020 03 7;42(3):e1900180. Epub 2020 Jan 7.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, P. R. China.

The cellular internal ribosomal entry site (IRES) is one of the most important elements to mediate cap-independent translational initiation, especially under conditions of stress and pathology. However, a high-throughput method to discover IRESs in these conditions is still lacking. Here, a possible way IRES long-read sequencing based on the latest high-throughput technologies is proposed to solve this problem. Read More

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Exon-Mediated Activation of Transcription Starts.

Cell 2019 12 28;179(7):1551-1565.e17. Epub 2019 Nov 28.

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02138, USA. Electronic address:

The processing of RNA transcripts from mammalian genes occurs in proximity to their transcription. Here, we describe a phenomenon affecting thousands of genes that we call exon-mediated activation of transcription starts (EMATS), in which the splicing of internal exons impacts promoter choice and the expression level of the gene. We observed that evolutionary gain of internal exons is associated with gain of new transcription start sites (TSSs) nearby and increased gene expression. Read More

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December 2019

Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast.

Genome Res 2019 12 18;29(12):1974-1984. Epub 2019 Nov 18.

SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 65 Solna, Sweden.

Cryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site (TSS) usage, chromatin organization, and posttranscriptional consequences in We show that TSSs of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality, and chromatin accessibility. We define the 5' and 3' boundaries of cryptic transcripts and show that, contrary to RNA degradation-sensitive ones, they often overlap with the end of the gene, thereby using the canonical polyadenylation site, and associate to polyribosomes. Read More

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December 2019

Two novel transcriptional reporter systems for monitoring Helicobacter pylori stress responses.

Plasmid 2019 11 1;106:102442. Epub 2019 Nov 1.

Federal Research Clinical Center of Physical-Chemical Medicine, Federal Medical and Biological Agency of Russia, Moscow 119435, Russia.

Helicobacter pylori, a human pathogen linked to many stomach diseases, is well adapted to colonize aggressive gastric environments, and its virulence factors contribute this adaptation. Here, we report the construction of two novel H. pylori vectors, pSv2 and pSv4, carrying a reporter gene fused to the promoters of virulence factor genes for monitoring the response of single H. Read More

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November 2019

The MarR-Type Regulator MalR Is Involved in Stress-Responsive Cell Envelope Remodeling in .

Front Microbiol 2019 21;10:1039. Epub 2019 May 21.

Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, Jülich, Germany.

It is the enormous adaptive capacity of microorganisms, which is key to their competitive success in nature, but also challenges antibiotic treatment of human diseases. To deal with a diverse set of stresses, bacteria are able to reprogram gene expression using a wide variety of transcription factors. Here, we focused on the MarR-type regulator MalR conserved in the , including the prominent pathogens and . Read More

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Fob1p recruits DNA topoisomerase I to ribosomal genes locus and contributes to its transcriptional silencing maintenance.

Int J Biochem Cell Biol 2019 05 14;110:143-148. Epub 2019 Mar 14.

Dipartimento di Biologia e Biotecnologie, Università di Roma, La Sapienza, Piazzale A. Moro 5, 00185, Roma, Italy; Istituto di Biologia e Patologia Molecolari, CNR, c/o Dipartimento di Biologia e Biotecnologie, Università di Roma, La Sapienza, Piazzale A. Moro 5, 00185, Roma, Italy. Electronic address:

S. cerevisiae ribosomal DNA (rDNA) locus hosts a series of highly complex regulatory machineries for RNA polymerase I, II and III transcription, DNA replication and units recombination, all acting in the Non Transcribed Spacers (NTSs) interposed between the repeated units by which it is composed. DNA topoisomerase I (Top1p) contributes, recruiting Sir2p, to the maintenance of transcriptional silencing occurring at the RNA Polymerase II cryptic promoters, located in the NTS region. Read More

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Contribution of spurious transcription to intellectual disability disorders.

J Med Genet 2019 08 11;56(8):491-498. Epub 2019 Feb 11.

Molecular Neurobiology and Neuropathology Unit, Instituto de Neurociencias (UMH-CSIC), San Juan de Alicante, Alicante, Spain.

During the development of multicellular organisms, chromatin-modifying enzymes orchestrate the establishment of gene expression programmes that characterise each differentiated cell type. These enzymes also contribute to the maintenance of cell type-specific transcription profiles throughout life. But what happens when epigenomic regulation goes awry? Genomic screens in experimental models of intellectual disability disorders (IDDs) caused by mutations in epigenetic machinery-encoding genes have shown that transcriptional dysregulation constitutes a hallmark of these conditions. Read More

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Engineered Strains for Optimal Identification and Expression of Cryptic Biosynthetic Gene Clusters.

Front Microbiol 2018 10;9:3042. Epub 2018 Dec 10.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

is a suitable host for the heterologous expression of biosynthetic gene clusters (BGCs) from actinomycetes to discover "cryptic" secondary metabolites. To improve the heterologous expression of BGCs, herein we optimized strain SBT5 via the stepwise integration of three global regulatory genes and two codon-optimized multi-drug efflux pump genes and deletion of a negative regulatory gene, yielding four engineered strains. All optimization steps were observed to promote the heterologous production of polyketides, non-ribosomal peptides, and hybrid antibiotics. Read More

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December 2018

Repression of Divergent Noncoding Transcription by a Sequence-Specific Transcription Factor.

Mol Cell 2018 12;72(6):942-954.e7

Cell Fate and Gene Regulation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

Many active eukaryotic gene promoters exhibit divergent noncoding transcription, but the mechanisms restricting expression of these transcripts are not well understood. Here, we demonstrate how a sequence-specific transcription factor represses divergent noncoding transcription at highly expressed genes in yeast. We find that depletion of the transcription factor Rap1 induces noncoding transcription in a large fraction of Rap1-regulated gene promoters. Read More

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December 2018

Using Lipoamidase as a Novel Probe To Interrogate the Importance of Lipoylation in Plasmodium falciparum.

mBio 2018 11 20;9(6). Epub 2018 Nov 20.

W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Lipoate is a redox active cofactor that is covalently bound to key enzymes of oxidative metabolism. is auxotrophic for lipoate during the intraerythrocytic stages, but it is not known whether lipoate attachment to protein is required or whether attachment is required in a specific subcellular compartment of the parasite. To address these questions, we used an enzyme called lipoamidase (Lpa) as a probe of lipoate metabolism. Read More

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November 2018

LTRs activated by Epstein-Barr virus-induced transformation of B cells alter the transcriptome.

Genome Res 2018 12 31;28(12):1791-1798. Epub 2018 Oct 31.

Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, California 91010, USA.

Endogenous retroviruses (ERVs) are ancient viral elements that have accumulated in the genome through retrotransposition events. Although they have lost their ability to transpose, many of the long terminal repeats (LTRs) that originally flanked full-length ERVs maintain the ability to regulate transcription. While these elements are typically repressed in somatic cells, they can function as transcriptional enhancers and promoters when this repression is lost. Read More

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December 2018

A Reverse Genetics System for Zika Virus Based on a Simple Molecular Cloning Strategy.

Viruses 2018 07 12;10(7). Epub 2018 Jul 12.

Department of Infectious Diseases, Molecular Virology, Heidelberg University, Centre for Integrative Infectious Disease Research, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany.

The Zika virus (ZIKV) has recently attracted major research interest as infection was unexpectedly associated with neurological manifestations in developing foetuses and with Guillain-Barré syndrome in infected adults. Understanding the underlying molecular mechanisms requires reverse genetic systems, which allow manipulation of infectious cDNA clones at will. In the case of flaviviruses, to which ZIKV belongs, several reports have indicated that the construction of full-length cDNA clones is difficult due to toxicity during plasmid amplification in . Read More

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Casein kinase 2 mediated phosphorylation of Spt6 modulates histone dynamics and regulates spurious transcription.

Nucleic Acids Res 2018 09;46(15):7612-7630

Laval University Cancer Research Center, St-Patrick Research Group in Basic Oncology, Québec, Québec, Canada.

CK2 is an essential protein kinase implicated in various cellular processes. In this study, we address a potential role of this kinase in chromatin modulations associated with transcription. We found that CK2 depletion from yeast cells leads to replication-independent increase of histone H3K56 acetylation and global activation of H3 turnover in coding regions. Read More

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September 2018

Discovery of recombinases enables genome mining of cryptic biosynthetic gene clusters in Burkholderiales species.

Proc Natl Acad Sci U S A 2018 05 16;115(18):E4255-E4263. Epub 2018 Apr 16.

Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, 266237 Qingdao, China;

Bacterial genomes encode numerous cryptic biosynthetic gene clusters (BGCs) that represent a largely untapped source of drugs or pesticides. Mining of the cryptic products is limited by the unavailability of streamlined genetic tools in native producers. Precise genome engineering using bacteriophage recombinases is particularly useful for genome mining. Read More

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Reactivation of endogenous retroviral elements via treatment with DNMT- and HDAC-inhibitors.

Cell Cycle 2018 30;17(7):811-822. Epub 2018 Apr 30.

a Division of Epigenomics and Cancer Risk Factors , German Cancer Research Center , Heidelberg , Germany.

Inhibitors of DNA methyltransferases (DNMTis) or histone deacetylases (HDACis) are epigenetic drugs which are investigated since decades. Several have been approved and are applied in the treatment of hematopoietic and lymphatic malignancies, although their mode of action has not been fully understood. Two recent findings improved mechanistic insights: i) activation of human endogenous retroviral elements (HERVs) with concomitant synthesis of double-stranded RNAs (dsRNAs), and ii) massive activation of promoters from long terminal repeats (LTRs) which originated from past HERV invasions. Read More

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December 2019

Gcn4 Binding in Coding Regions Can Activate Internal and Canonical 5' Promoters in Yeast.

Mol Cell 2018 04 5;70(2):297-311.e4. Epub 2018 Apr 5.

Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Electronic address:

Gcn4 is a yeast transcriptional activator induced by amino acid starvation. ChIP-seq analysis revealed 546 genomic sites occupied by Gcn4 in starved cells, representing ∼30% of Gcn4-binding motifs. Surprisingly, only ∼40% of the bound sites are in promoters, of which only ∼60% activate transcription, indicating extensive negative control over Gcn4 function. Read More

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Distinct core promoter codes drive transcription initiation at key developmental transitions in a marine chordate.

BMC Genomics 2018 02 26;19(1):164. Epub 2018 Feb 26.

Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen, N-5006, Norway.

Background: Development is largely driven by transitions between transcriptional programs. The initiation of transcription at appropriate sites in the genome is a key component of this and yet few rules governing selection are known. Here, we used cap analysis of gene expression (CAGE) to generate bp-resolution maps of transcription start sites (TSSs) across the genome of Oikopleura dioica, a member of the closest living relatives to vertebrates. Read More

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February 2018