310 results match your criteria promoters telomeres

In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood.

Life Sci Alliance 2021 06 9;4(6). Epub 2021 Apr 9.

University of Rennes, EHESP, Inserm, Institut de Recherche en Santé, Environnement et Travail (Irset)-UMR_S 1085, Rennes, France

Environmental factors can induce detrimental consequences into adulthood life. In this study, we examined the epigenetic effects induced by in utero chlordecone (CD) exposure on human male cord blood as well as in blood-derived Ke-37 cell line. Genome-wide analysis of histone H3K4me3 distribution revealed that genes related to chromosome segregation, chromatin organization, and cell cycle have altered occupancy in their promoters. Read More

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G-quadruplexes: a promising target for cancer therapy.

Mol Cancer 2021 02 25;20(1):40. Epub 2021 Feb 25.

Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, 53127, Bonn, Germany.

DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). Read More

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February 2021

Recent Developments in Small-Molecule Ligands of Medicinal Relevance for Harnessing the Anticancer Potential of G-Quadruplexes.

Molecules 2021 Feb 5;26(4). Epub 2021 Feb 5.

Department of Chemistry, University of Cyprus, 1 Panepistimiou Avenue, 2109 Nicosia, Cyprus.

G-quadruplexes, a family of tetraplex helical nucleic acid topologies, have emerged in recent years as novel targets, with untapped potential for anticancer research. Their potential stems from the fact that G-quadruplexes occur in functionally-important regions of the human genome, such as the telomere tandem sequences, several proto-oncogene promoters, other regulatory regions and sequences of DNA (e.g. Read More

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February 2021

Learning to Model G-Quadruplexes: Current Methods and Perspectives.

Annu Rev Biophys 2021 May 9;50:209-243. Epub 2021 Feb 9.

CIC nanoGUNE BRTA, 20018 Donostia, Euskadi, Spain; email:

G-quadruplexes have raised considerable interest during the past years for the development of therapies against cancer. These noncanonical structures of DNA may be found in telomeres and/or oncogene promoters, and it has been observed that the stabilization of such G-quadruplexes may disturb tumor cell growth. Nevertheless, the mechanisms leading to folding and stabilization of these G-quadruplexes are still not well established, and they are the focus of much current work in this field. Read More

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Exploring TERRA during Leishmania major developmental cycle and continuous in vitro passages.

Int J Biol Macromol 2021 Mar 3;174:573-586. Epub 2021 Feb 3.

Department of Chemical and Biological Sciences, Biosciences Institute, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil. Electronic address:

Telomeres from different eukaryotes, including trypanosomatids, are transcribed into TERRA noncoding RNAs, crucial in regulating chromatin deposition and telomere length. TERRA is transcribed from the C-rich subtelomeric strand towards the 3'-ends of the telomeric array. Using bioinformatics, we confirmed the presence of subtelomeric splice acceptor sites at all L. Read More

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Febrile temperature causes transcriptional downregulation of Plasmodium falciparum Sirtuins through Hsp90-dependent epigenetic modification.

Mol Microbiol 2021 Feb 4. Epub 2021 Feb 4.

Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India.

Sirtuins (PfSIR2A and PfSIR2B) are implicated to play pivotal roles in the silencing of sub-telomeric genes and the maintenance of telomere length in P. falciparum 3D7 strain. Here, we identify the key factors that regulate the cellular abundance and activity of these two histone deacetylases. Read More

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February 2021

RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions.

Cell Rep 2020 12;33(12):108546

The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

Regulator of telomere length 1 (RTEL1) is an essential helicase that maintains telomere integrity and facilitates DNA replication. The source of replication stress in Rtel1-deficient cells remains unclear. Here, we report that loss of RTEL1 confers extensive transcriptional changes independent of its roles at telomeres. Read More

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December 2020

Non-duplex G-Quadruplex DNA Structure: A Developing Story from Predicted Sequences to DNA Structure-Dependent Epigenetics and Beyond.

Acc Chem Res 2021 01 21;54(1):46-56. Epub 2020 Dec 21.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

The story of the non-duplex DNA form known as the G-quadruplex (G4) has traversed a winding path. From initial skepticism followed by debate to a surge in interest, the G4 story intertwines many threads. Starting with computational predictions of a gene regulatory role, which now include epigenetic functions, our group was involved in many of these advances along with many other laboratories. Read More

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January 2021

G-Quadruplex loops regulate PARP-1 enzymatic activation.

Nucleic Acids Res 2021 01;49(1):416-431

Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

G-Quadruplexes are non-B form DNA structures present at regulatory regions in the genome, such as promoters of proto-oncogenes and telomeres. The prominence in such sites suggests G-quadruplexes serve an important regulatory role in the cell. Indeed, oxidized G-quadruplexes found at regulatory sites are regarded as epigenetic elements and are associated with an interlinking of DNA repair and transcription. Read More

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January 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: Triggering a Lethal Fight to Keep Control of the Ten-Eleven Translocase (TET)-Associated DNA Demethylation?

Pathogens 2020 Nov 30;9(12). Epub 2020 Nov 30.

Institute of Physical Chemistry, University of Münster, 481 49 Münster, Germany.

The extended and diverse interference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in multiple host functions and the diverse associated symptoms implicate its involvement in fundamental cellular regulatory processes. The activity of ten-eleven translocase 2 (TET2) responsible for selective DNA demethylation, has been recently identified as a regulator of endogenous virus inactivation and viral invasion, possibly by proteasomal deregulation of the TET2/TET3 activities. In a recent report, we presented a detailed list of factors that can be affected by TET activity, including recognition of zinc finger protein binding sites and bimodal promoters, by enhancing the flexibility of adjacent sequences. Read More

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November 2020

TERT promoter alterations could provide a solution for Peto's paradox in rodents.

Sci Rep 2020 11 30;10(1):20815. Epub 2020 Nov 30.

Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.

Cancer is a genetic disease caused by changes in gene expression resulting from somatic mutations and epigenetic changes. Although the probability of mutations is proportional with cell number and replication cycles, large bodied species do not develop cancer more frequently than smaller ones. This notion is known as Peto's paradox, and assumes stronger tumor suppression in larger animals. Read More

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November 2020

Biophysical and X-ray structural studies of the (GGGTT)3GGG G-quadruplex in complex with N-methyl mesoporphyrin IX.

PLoS One 2020 18;15(11):e0241513. Epub 2020 Nov 18.

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.

The G-quadruplex (GQ) is a well-studied non-canonical DNA structure formed by G-rich sequences found at telomeres and gene promoters. Biological studies suggest that GQs may play roles in regulating gene expression, DNA replication, and DNA repair. Small molecule ligands were shown to alter GQ structure and stability and thereby serve as novel therapies, particularly against cancer. Read More

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December 2020

Topological conversion of human telomeric G-quadruplexes from hybrid to parallel form induced by naphthalene diimide ligands.

Int J Biol Macromol 2021 Jan 11;167:1048-1058. Epub 2020 Nov 11.

Laboratory of Polymer Composite and Engineering, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramolecular GQs. Here we report the topological conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K solution. Read More

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January 2021

G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders.

Nucleic Acids Res 2020 12;48(21):11942-11957

Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Selmi 3, 40126 Bologna, Italy.

Genomic DNA and cellular RNAs can form a variety of non-B secondary structures, including G-quadruplex (G4) and R-loops. G4s are constituted by stacked guanine tetrads held together by Hoogsteen hydrogen bonds and can form at key regulatory sites of eukaryote genomes and transcripts, including gene promoters, untranslated exon regions and telomeres. R-loops are 3-stranded structures wherein the two strands of a DNA duplex are melted and one of them is annealed to an RNA. Read More

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December 2020

G4 Structures in Control of Replication and Transcription of rRNA Genes.

Front Plant Sci 2020 8;11:593692. Epub 2020 Oct 8.

Laboratory of Functional Genomics and Proteomics, National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czechia.

Genes encoding 45S ribosomal RNA (rDNA) are known for their abundance within eukaryotic genomes and for their unstable copy numbers in response to changes in various genetic and epigenetic factors. Commonly, we understand as epigenetic factors (affecting gene expression without a change in DNA sequence), namely DNA methylation, histone posttranslational modifications, histone variants, RNA interference, nucleosome remodeling and assembly, and chromosome position effect. All these were actually shown to affect activity and stability of rDNA. Read More

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October 2020

PAR-TERRA is the main contributor to telomeric repeat-containing RNA transcripts in normal and cancer mouse cells.

RNA 2021 01 30;27(1):106-121. Epub 2020 Oct 30.

Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.

Telomeric repeat-containing RNA (TERRA) molecules play important roles at telomeres, from heterochromatin regulation to telomerase activity control. In human cells, TERRA is transcribed from subtelomeric promoters located on most chromosome ends and associates with telomeres. The origin of mouse TERRA molecules is, however, unclear, as transcription from the pseudoautosomal PAR locus was recently suggested to account for the vast majority of TERRA in embryonic stem cells (ESC). Read More

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January 2021

Regulation of telomeric function by DNA methylation differs between humans and mice.

Hum Mol Genet 2020 Nov;29(19):3197-3210

Department of Genetics, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 31096, Israel.

The most distal 2 kb region in the majority of human subtelomeres contains CpG-rich promoters for TERRA, a long non-coding RNA. When the function of the de novo DNA methyltransferase DNMT3B is disrupted, as in ICF1 syndrome, subtelomeres are abnormally hypomethylated, subtelomeric heterochromatin acquires open chromatin characteristics, TERRA is highly expressed, and telomeres shorten rapidly. In this study, we explored whether the regulation of subtelomeric epigenetic characteristics by DNMT3B is conserved between humans and mice. Read More

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November 2020

G-quadruplex ligands targeting telomeres do not inhibit HIV promoter activity and cooperate with latency reversing agents in killing latently infected cells.

Cell Cycle 2020 09 17;19(18):2298-2313. Epub 2020 Aug 17.

Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester , Rochester, NY, USA.

Altered telomere maintenance mechanism (TMM) is linked to increased DNA damage at telomeres and telomere uncapping. We previously showed that HIV-1 latent cells have altered TMM and are susceptible to ligands that target G-quadruplexes (G4) at telomeres. Susceptibility of latent cells to telomere targeting could potentially be used to support approaches to eradicate HIV reservoirs. Read More

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September 2020

ZSCAN4 facilitates chromatin remodeling and promotes the cancer stem cell phenotype.

Oncogene 2020 06 7;39(26):4970-4982. Epub 2020 Jun 7.

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Cancer stem cells (CSCs) are cells within tumors that maintain the ability to self-renew, drive tumor growth, and contribute to therapeutic resistance and cancer recurrence. In this study, we investigate the role of Zinc finger and SCAN domain containing 4 (ZSCAN4) in human head and neck squamous cell carcinoma (HNSCC). The murine Zscan4 is involved in telomere maintenance and genomic stability of mouse embryonic stem cells. Read More

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Epigenetic Features of Human Perinatal Stem Cells Redefine Their Stemness Potential.

Cells 2020 05 24;9(5). Epub 2020 May 24.

Department of Medicine and Aging Sciences, "G. D'Annunzio" University of Chieti- Pescara, 66100 Chieti, Italy.

Human perinatal stem cells (SCs) can be isolated from fetal annexes without ethical or safety limitations. They are generally considered multipotent; nevertheless, their biological characteristics are still not fully understood. The aim of this study was to investigate the pluripotency potential of human perinatal SCs as compared to human induced pluripotent stem cells (hiPSCs). Read More

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Photoactivated semi-synthetic derivative of osajin selectively interacts with G-quadruplex DNA.

Nat Prod Res 2020 May 18:1-6. Epub 2020 May 18.

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Natural and synthetic small molecules targeting G-quadruplex are currently being studied. These peculiar DNA arrangements arise in guanine-rich sequences located in telomeres, oncogene promoters and in several viruses. Two semi-synthetic derivatives of osajin, a natural isoflavone from , were prepared and screened for their binding affinity towards G-quadruplex and double stranded DNA (dsDNA) using electrospray mass spectrometry (ESI-MS). Read More

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Telomerase Reverse Transcriptase Promoter Mutations Identify a Genomically Defined and Highly Aggressive Human Pleural Mesothelioma Subgroup.

Clin Cancer Res 2020 07 21;26(14):3819-3830. Epub 2020 Apr 21.

Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Purpose: Human malignant pleural mesothelioma (MPM) is characterized by dismal prognosis. Consequently, dissection of molecular mechanisms driving malignancy is of key importance. Here we investigate whether activating mutations in the telomerase reverse transcriptase () gene promoter are present in MPM and associated with disease progression, cell immortalization, and genomic alteration patterns. Read More

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Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment.

Elife 2020 04 16;9. Epub 2020 Apr 16.

Institut de Recherche en Immunologie et Cancérologie (IRIC), Département de biologie moléculaire, Faculté de Médecine, Université de Montréal, Montréal, Canada.

The precise relationship between epigenetic alterations and telomere dysfunction is still an extant question. Previously, we showed that eroded telomeres lead to differentiation instability in murine embryonic stem cells (mESCs) via DNA hypomethylation at pluripotency-factor promoters. Here, we uncovered that telomerase reverse transcriptase null () mESCs exhibit genome-wide alterations in chromatin accessibility and gene expression during differentiation. Read More

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Human subtelomeric DNA methylation: regulation and roles in telomere function.

Curr Opin Genet Dev 2020 02 25;60:9-16. Epub 2020 Feb 25.

Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel. Electronic address:

Subtelomeres are the regions at chromosome ends, immediately adjacent to the terminal telomeric repeats. The majority of human subtelomeres are CpG-rich in their distal two kilobases, and are methylated during early embryonic development by the de novo DNA methyltransferase DNMT3B. The biological relevance of subtelomeric DNA methylation is highlighted by the presence of promoters for the long non-coding TERRA transcripts in these CpG-rich regions. Read More

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February 2020

Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization.

J Am Chem Soc 2020 02 28;142(6):2876-2888. Epub 2020 Jan 28.

Department of Medical Biochemistry and Biophysics , Umeå University , Umeå 90736 , Sweden.

The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Read More

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February 2020

Engineering the Promoter of for Enhanced Protein Production by Replacing the Binding Sites of a Transcription Repressor ACE1 to Those of the Activators.

J Agric Food Chem 2020 Feb 21;68(5):1337-1346. Epub 2020 Jan 21.

Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute , Chinese Academy of Agricultural Sciences , Beijing 100081 , China.

The strong and inducible promoter is most widely used to express heterologous proteins, useful in food and feed industries, in . Enhancing its ability to direct transcription provides a general strategy to improve protein production in . The promoter was engineered by replacing eight binding sites of the transcription repressor ACE1 to those of the activators ACE2, Hap2/3/5, and Xyr1. Read More

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February 2020

Same fold, different properties: polarizable molecular dynamics simulations of telomeric and TERRA G-quadruplexes.

Justin A Lemkul

Nucleic Acids Res 2020 01;48(2):561-575

Department of Biochemistry and Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, USA.

DNA and RNA sequences rich in guanine can fold into noncanonical structures called G-quadruplexes (GQs), which exhibit a common stem structure of Hoogsteen hydrogen-bonded guanine tetrads and diverse loop structures. GQ sequence motifs are overrepresented in promoters, origins of replication, telomeres, and untranslated regions in mRNA, suggesting roles in modulating gene expression and preserving genomic integrity. Given these roles and unique aspects of different structures, GQs are attractive targets for drug design, but greater insight into GQ folding pathways and the interactions stabilizing them is required. Read More

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January 2020

From the wings to the center stage of chromosomes.

J Biol Chem 2019 11;294(47):17723-17724

Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan

Telomere-binding protein TRF2 protects the linear chromosome ends, telomeres, from being recognized as damaged DNA. TRF2 also regulates gene expression outside telomeres, but the detailed mechanism has not been fully understood. Mukherjee and colleagues have employed ChIP-Seq and biochemical analyses to identify G-quadruplexes at gene promoters across the genome as nontelomeric TRF2-binding sites. Read More

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November 2019

Rap1-mediated nucleosome displacement can regulate gene expression in senescent cells without impacting the pace of senescence.

Aging Cell 2020 01 19;19(1):e13061. Epub 2019 Nov 19.

Department of Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, USA.

Cell senescence is accompanied, and in part mediated, by changes in chromatin, including histone losses, but underlying mechanisms are not well understood. We reported previously that during yeast cell senescence driven by telomere shortening, the telomeric protein Rap1 plays a major role in reprogramming gene expression by relocalizing hundreds of new target genes (called NRTS, for new Rap1 targets at senescence) to the promoters. This leads to two types of histone loss: Rap1 lowers histone level globally by repressing histone gene expression, and it also causes local nucleosome displacement at the promoters of upregulated NRTS. Read More

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January 2020