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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.

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

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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