Publications
52 results found
Hansel-Hertsch R, Beraldi D, Lensing SV, et al., 2016, G-quadruplex structures mark human regulatory chromatin, Nature Genetics, Vol: 48, Pages: 1267-1272, ISSN: 1061-4036
G-quadruplex (G4) structural motifs have been linked to transcription1,2, replication3 and genome instability4,5 and are implicated in cancer and other diseases6,7,8. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context9,10. Herein we address this through the development of G4 ChIP–seq, an antibody-based G4 chromatin immunoprecipitation and high-throughput sequencing approach. We find ∼10,000 G4 structures in human chromatin, predominantly in regulatory, nucleosome-depleted regions. G4 structures are enriched in the promoters and 5′ UTRs of highly transcribed genes, particularly in genes related to cancer and in somatic copy number amplifications, such as MYC. Strikingly, de novo and enhanced G4 formation are associated with increased transcriptional activity, as shown by HDAC inhibitor–induced chromatin relaxation and observed in immortalized as compared to normal cellular states. Our findings show that regulatory, nucleosome-depleted chromatin and elevated transcription shape the endogenous human G4 DNA landscape.
Chambers VS, Marsico G, Boutell JM, et al., 2015, High-throughput sequencing of DNA G-quadruplex structures in the human genome, Nature Biotechnology, Vol: 33, Pages: 877-881, ISSN: 1087-0156
G-quadruplexes (G4s) are nucleic acid secondary structures that form within guanine-rich DNA or RNA sequences. G4 formation can affect chromatin architecture and gene regulation and has been associated with genomic instability, genetic diseases and cancer progression1,2,3,4. Here we present a high-resolution sequencing–based method to detect G4s in the human genome. We identified 716,310 distinct G4 structures, 451,646 of which were not predicted by computational methods5,6,7. These included previously uncharacterized noncanonical long loop and bulged structures8,9. We observed a high G4 density in functional regions, such as 5′ untranslated regions and splicing sites, as well as in genes previously not predicted to contain these structures (such as BRCA2). G4 formation was significantly associated with oncogenes, tumor suppressors and somatic copy number alterations related to cancer development10. The G4s identified in this study may therefore represent promising targets for cancer intervention.
Yangyuoru PM, DiAntonio M, Ghimire C, et al., 2015, Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G‐Quadruplex, Angewandte Chemie, Vol: 127, Pages: 924-927, ISSN: 0044-8249
<jats:title>Abstract</jats:title><jats:p>In investigating the binding interactions between the human telomeric RNA (TERRA) G‐quadruplex (GQ) and its ligands, it was found that the small molecule carboxypyridostatin (cPDS) and the GQ‐selective antibody BG4 simultaneously bind the TERRA GQ. We previously showed that the overall binding affinity of BG4 for RNA GQs is not significantly affected in the presence of cPDS. However, single‐molecule mechanical unfolding experiments revealed a population (48 %) with substantially increased mechanical and thermodynamic stability. Force‐jump kinetic investigations suggested competitive binding of cPDS and BG4 to the TERRA GQ. Following this, the two bound ligands slowly rearrange, thereby leading to the minor population with increased stability. Given the relevance of G‐quadruplexes in the regulation of biological processes, we anticipate that the unprecedented conformational rearrangement observed in the TERRA‐GQ–ligand complex may inspire new strategies for the selective stabilization of G‐quadruplexes in cells.</jats:p>
Yangyuoru PM, Di Antonio M, Ghimire C, et al., 2015, Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 54, Pages: 910-913, ISSN: 1433-7851
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- Citations: 25
Le DD, Di Antonio M, Chan LKM, et al., 2015, G-quadruplex ligands exhibit differential G-tetrad selectivity, CHEMICAL COMMUNICATIONS, Vol: 51, Pages: 8048-8050, ISSN: 1359-7345
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- Citations: 70
Di Antonio M, McLuckie KIE, Balasubramanian S, 2014, Reprogramming the Mechanism of Action of Chlorambucil by Coupling to a G-Quadruplex Ligand, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 136, Pages: 5860-5863, ISSN: 0002-7863
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- Citations: 52
Biffi G, Di Antonio M, Tannahill D, et al., 2014, Visualization and selective chemical targeting of RNA G-quadruplex structures in the cytoplasm of human cells, NATURE CHEMISTRY, Vol: 6, Pages: 75-80, ISSN: 1755-4330
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- Citations: 435
Di Antonio M, 2014, Quinone Methides Generation: Applications in Chemical Biology, CURRENT ORGANIC CHEMISTRY, Vol: 18, Pages: 2-2, ISSN: 1385-2728
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- Citations: 2
McLuckie KIE, Di Antonio M, Zecchini H, et al., 2013, G-Quadruplex DNA as a Molecular Target for Induced Synthetic Lethality in Cancer Cells, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 135, Pages: 9640-9643, ISSN: 0002-7863
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- Citations: 103
Mitchell T, Ramos-Montoya A, Di Antonio M, et al., 2013, Downregulation of Androgen Receptor Transcription by Promoter G-Quadruplex Stabilization as a Potential Alternative Treatment for Castrate-Resistant Prostate Cancer, BIOCHEMISTRY, Vol: 52, Pages: 1429-1436, ISSN: 0006-2960
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- Citations: 21
Nikan M, Di Antonio M, Abecassis K, et al., 2013, An Acetylene-Bridged 6,8-Purine Dimer as a Fluorescent Switch-On Probe for Parallel G-Quadruplexes, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 52, Pages: 1428-1431, ISSN: 1433-7851
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- Citations: 42
Murat P, Gormally MV, Sanders D, et al., 2013, Light-mediated <i>in cell</i> downregulation of G-quadruplex-containing genes using a photo-caged ligand, CHEMICAL COMMUNICATIONS, Vol: 49, Pages: 8453-8455, ISSN: 1359-7345
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- Citations: 27
Di Antonio M, Rodriguez R, Balasubramanian S, 2012, Experimental approaches to identify cellular G-quadruplex structures and functions, METHODS, Vol: 57, Pages: 84-92, ISSN: 1046-2023
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- Citations: 38
Di Antonio M, Biffi G, Mariani A, et al., 2012, Selective RNA Versus DNA G-Quadruplex Targeting by In Situ Click Chemistry, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 51, Pages: 11073-11078, ISSN: 1433-7851
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- Citations: 132
Doria F, Nadai M, Folini M, et al., 2012, Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 10, Pages: 2798-2806, ISSN: 1477-0520
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- Citations: 90
Mueller S, Sanders DA, Di Antonio M, et al., 2012, Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 10, Pages: 6537-6546, ISSN: 1477-0520
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- Citations: 100
Nadai M, Doria F, Di Antonio M, et al., 2011, Naphthalene diimide scaffolds with dual reversible and covalent interaction properties towards G-quadruplex, BIOCHIMIE, Vol: 93, Pages: 1328-1340, ISSN: 0300-9084
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- Citations: 80
Percivalle C, La Rosa A, Verga D, et al., 2011, Quinone Methide Generation via Photoinduced Electron Transfer, JOURNAL OF ORGANIC CHEMISTRY, Vol: 76, Pages: 3096-3106, ISSN: 0022-3263
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- Citations: 41
Verga D, Nadai M, Doria F, et al., 2010, Photogeneration and Reactivity of Naphthoquinone Methides as Purine Selective DNA Alkylating Agents, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 132, Pages: 14625-14637, ISSN: 0002-7863
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- Citations: 90
Doria F, di Antonio M, Benotti M, et al., 2009, Substituted Heterocyclic Naphthalene Diimides with Unexpected Acidity. Synthesis, Properties, and Reactivity, JOURNAL OF ORGANIC CHEMISTRY, Vol: 74, Pages: 8616-8625, ISSN: 0022-3263
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- Citations: 48
Di Antonio M, Doria F, Richter SN, et al., 2009, Quinone Methides Tethered to Naphthalene Diimides as Selective G-Quadruplex Alkylating Agents, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 131, Pages: 13132-13141, ISSN: 0002-7863
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- Citations: 128
Di Antonio M, Doria F, Mella M, et al., 2007, Novel naphthalene diimides as activatable precursors of bisalkylating agents, by reduction and base catalysis, JOURNAL OF ORGANIC CHEMISTRY, Vol: 72, Pages: 8354-8360, ISSN: 0022-3263
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- Citations: 33
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