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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.

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

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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