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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.

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

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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