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XPGCS SIGNED

Single cell profiling of X chromosome reactivation during primordial germ cell specification in vivo

Total Cost €

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EC-Contrib. €

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Partnership

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 XPGCS project word cloud

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

provides    precursors    castaneus    model    undergoes    chromatin    gene    genomic    epigenetic    cell    mice    innovative    demethylase    hybrid    genders    kinetics    plays    global    reprogramming    pgcs    chromosome    single    strains    compensation    specification    sperm    polymorphisms    methylation    maternal    pgc    coating    biallelic    inactivation    histone    altogether    sequence    monitoring    female    parallel    unravel    xp    allele    genetic    generations    mechanisms    multidisciplinary    extensive    mutant    paternal    genes    explore    dynamics    mark    coding    mouse    mapped    conjunction    rate    linked    h3k27me3    conditional    cells    erasure    enrichment    chromosomes    insights    germ    c57bl    entire    repressive    roles    perform    dosage    inactivated    transmit    utx    inactive    xci    xi    rna    progressive    f1    xist    regulation    reactivation    initiation    germline    eggs    transcriptome    expression    imprints    primordial    xm    followed    little    subsequent    embryos   

Project "XPGCS" 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]
 Project website https://www.gurdon.cam.ac.uk/research/surani
 Total cost 195˙454 €
 EC max contribution 195˙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-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2018-04-17

 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 195˙454.00

Map

 Project objective

In female mice, one of the two X chromosomes is inactivated during early development to ensure dosage compensation between genders. A long non-coding gene, Xist, plays a crucial role in the initiation of the X chromosome inactivation (XCI) process. Primordial germ cells (PGCs), the precursors of sperm and eggs, transmit genetic and epigenetic information to subsequent generations, following extensive reprogramming, erasure of methylation and genomic imprints, and X chromosome reactivation. The inactive X (Xi) then undergoes progressive reprogramming and reactivation in the germline of female embryos, through the loss of Xist RNA coating, followed by the erasure of the repressive H3K27me3 histone mark, and eventually biallelic expression of X-linked genes. Although the global dynamics of Xi reactivation have been mapped little is known about the gene-specific dynamics, or the mechanisms involved. To explore gene activity on the entire X chromosome during reprogramming in the germline, I will perform single-cell transcriptome analyses on PGCs from C57BL/6 X Castaneus F1 female hybrid embryos. The high rate of sequence polymorphisms between these strains provides allele-specific information for the activity of the Xp (paternal X) and the Xm (maternal X). I will investigate the kinetics of Xp and Xm gene reactivation chromosome-wide at the single cell level following PGC specification. Furthermore, I will study the dynamics of the expression of X-linked genes in conjunction with chromatin changes in PGCs by monitoring the loss of H3K27me3 enrichment on the inactive X chromosome. In parallel, I will study how the regulation of H3K27me3 affect Xi reactivation by using a conditional mutant mouse model of a H3K27me3 demethylase, UTX. Altogether, the innovative and multidisciplinary approach of this study will unravel important insights on germline reprogramming and the roles of chromatin changes associated with X chromosome reactivation.

 Publications

year authors and title journal last update
List of publications.
2018 Jan J Zylicz, Maud Borensztein, Frederick CK Wong, Yun Huang, Caroline Lee, Sabine Dietmann, M Azim Surani
G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.33361
eLife 7 2019-06-13
2017 Maud Borensztein, Ikuhiro Okamoto, Laurène Syx, Guillaume Guilbaud, Christel Picard, Katia Ancelin, Rafael Galupa, Patricia Diabangouaya, Nicolas Servant, Emmanuel Barillot, Azim Surani, Mitinori Saitou, Chong-Jian Chen, Konstantinos Anastassiadis, Edith Heard
Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-01415-5
Nature Communications 8/1 2019-06-13

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