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QAPs SIGNED

G-Quadruplex-associated proteins (QAPs) and their role in transcriptional regulation

Total Cost €

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EC-Contrib. €

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Partnership

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 QAPs project word cloud

Explore the words cloud of the QAPs project. It provides you a very rough idea of what is the project "QAPs" about.

human    interdisciplinary    functional    gene    mapped    sequences    genomic    visualized    replication    modulated    g4    little    chromatin    biochemical    native    consequence    antibodies    proteins    canonical    techniques    group    endogenous    cancer    transcriptional    anti    excellent    regulating    transcription    g4s    small    dna    stranded    seq    implicated    databases    elucidate    genetically    ligands    nuclei    instability    balasubramanian    regulatory    candidates    bioinformatics    recruitment    context    structures    generate    exploration    cruk    modes    molecule    binding    laboratories    interacting    form    mass    stabilising    chemistry    consecutive    rapid    identification    regulation    insights    linked    deficient    sequencing    stress    position    biology    mechanisms    training    secondary    dynamics    protein    marks    genome    cells    elevated    rime    interaction    agents    interactome    verify    throughput    ultimately    coupled    biophysical    chip    quadruplexes    immunofluorescence    spectrometry    immunoprecipitation    uk    cambridge    ci    regions   

Project "QAPs" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2019-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 183˙454.00

Map

 Project objective

In the human genome, many G-rich sequences have the potential to form 4-stranded non-canonical secondary structures known as G-quadruplexes (G4s). G4 structures have been visualized in nuclei by immunofluorescence and mapped genome-wide to regulatory chromatin regions linked to elevated transcription using G4 chromatin immunoprecipitation and high-throughput sequencing (G4 ChIP-seq). G4s are implicated in gene regulation, DNA replication and genome instability, yet little is known about their protein interaction partners or role in regulating genome activity. We therefore propose to develop G4 Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (G4 RIME) methodologies to elucidate the G4 interactome within a native chromatin context. ChIP-seq of protein candidates coupled with G4 ChIP-seq will verify binding at endogenous G4 structures. Using established biophysical and biochemical techniques, we will investigate binding modes, recruitment and effects on G4 dynamics. Consecutive chromatin immunoprecipitation steps using antibodies targeting characteristic chromatin marks as well as G4 ChIP-seq supported by bioinformatics analysis of genomic databases will identify proteins involved in transcriptional regulation. We will then test the consequence of stabilising G4s with small molecule ligands on the G4 interactome and how this is modulated during genomic stress. Cells genetically deficient in G4-interacting proteins will enable detailed exploration of G4 formation and transcriptional effects. This highly interdisciplinary project will provide a wide range of excellent training opportunities exploiting the Balasubramanian group’s unique position with laboratories at the Cancer Research UK Cambridge Institute (CRUK CI) and the Department of Chemistry. Overall, the studies will generate novel functional insights in the G4 biology that may ultimately lead to the identification of mechanisms and pathways for new anti-cancer agents.

 Publications

year authors and title journal last update
List of publications.
2018 Shi-Qing Mao, Avazeh T. Ghanbarian, Jochen Spiegel, Sergio Martínez Cuesta, Dario Beraldi, Marco Di Antonio, Giovanni Marsico, Robert Hänsel-Hertsch, David Tannahill, Shankar Balasubramanian
DNA G-quadruplex structures mold the DNA methylome
published pages: 951-957, ISSN: 1545-9993, DOI: 10.1038/s41594-018-0131-8
Nature Structural & Molecular Biology 25/10 2019-05-07
2018 Robert Hänsel-Hertsch, Jochen Spiegel, Giovanni Marsico, David Tannahill, Shankar Balasubramanian
Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing
published pages: 551-564, ISSN: 1754-2189, DOI: 10.1038/nprot.2017.150
Nature Protocols 13/3 2019-06-11

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