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XChromosome SIGNED

Functions of the X chromosome in the mammalian germ line

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Project "XChromosome" data sheet

The following table provides information about the project.

Coordinator
THE FRANCIS CRICK INSTITUTE LIMITED 

Organization address
address: 1 MIDLAND ROAD
city: LONDON
postcode: NW1 1AT
website: www.crick.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 1˙912˙369 €
 EC max contribution 1˙912˙369 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2021-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 1˙912˙369.00

Map

 Project objective

Male and female mammals differ in their sex chromosome complement: males have one X chromosome and one Y chromosome (XY), while females have two X chromosomes (XX). Decades of research have demonstrated that the Y chromosome is crucial for male fertility, regulating both sex differentiation and spermatogenesis. However, the role of the X chromosome in these critical stages of germ line development remains poorly understood.

In this proposal, we will explore the functions of the X chromosome in the mammalian germ line. In eutherian mammals, sex determination is dependent on the Y-gene Sry, but in the other major mammalian class, the metatherians, it is controlled not only by a Y-locus, but also by the complement of X chromosomes. In Aim 1 we will apply CRISPR-mediated genome editing to metatherian mammals in order to identify these critical X and Y sex-determining genes. Our findings will provide insight into mammalian sex chromosome evolution and the aetiology of human sex differentiation disorders.

In addition to its role in sex determination, the X chromosome is also predicted to become evolutionarily specialised for spermatogenesis. Consistent with this theory, we discovered that the mouse X chromosome is enriched in genes expressed exclusively in developing sperm. These genes are present in multiple copies, and together comprise an unprecedented 18% of the mouse X chromosome gene content. Many could be important candidates for unexplained male infertility. However, the functions of these genes have not been determined, because they cannot be manipulated using conventional gene targeting strategies. In Aim 2, we will use CRISPR to establish the roles of X-multicopy genes in male reproduction.

 Publications

year authors and title journal last update
List of publications.
2017 Elias ElInati, Helen R. Russell, Obah A. Ojarikre, Mahesh Sangrithi, Takayuki Hirota, Dirk G. de Rooij, Peter J. McKinnon, James M. A. Turner
DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line
published pages: 12536-12541, ISSN: 0027-8424, DOI: 10.1073/pnas.1712530114
Proceedings of the National Academy of Sciences 114/47 2020-01-24
2017 Mahesh N. Sangrithi, Helene Royo, Shantha K. Mahadevaiah, Obah Ojarikre, Leena Bhaw, Abdul Sesay, Antoine H.F.M. Peters, Michael Stadler, James M.A. Turner
Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline
published pages: 289-301.e3, ISSN: 1534-5807, DOI: 10.1016/j.devcel.2016.12.023
Developmental Cell 40/3 2020-01-24
2018 Mahesh N. Sangrithi, James M. A. Turner
Mammalian X Chromosome Dosage Compensation: Perspectives From the Germ Line
published pages: 1800024, ISSN: 0265-9247, DOI: 10.1002/bies.201800024
BioEssays 40/6 2020-01-24
2015 James M.A. Turner
Meiotic Silencing in Mammals
published pages: 395-412, ISSN: 0066-4197, DOI: 10.1146/annurev-genet-112414-055145
Annual Review of Genetics 49/1 2020-01-24
2017 Takayuki Hirota, Hiroshi Ohta, Benjamin E. Powell, Shantha K. Mahadevaiah, Obah A. Ojarikre, Mitinori Saitou, James M. A. Turner
Fertile offspring from sterile sex chromosome trisomic mice
published pages: 932-935, ISSN: 0036-8075, DOI: 10.1126/science.aam9046
Science 357/6354 2020-01-24
2018 Takayuki Hirota, Paul Blakeley, Mahesh N. Sangrithi, Shantha K. Mahadevaiah, Vesela Encheva, Ambrosius P. Snijders, Elias ElInati, Obah A. Ojarikre, Dirk G. de Rooij, Kathy K. Niakan, James M.A. Turner
SETDB1 Links the Meiotic DNA Damage Response to Sex Chromosome Silencing in Mice
published pages: 645-659.e6, ISSN: 1534-5807, DOI: 10.1016/j.devcel.2018.10.004
Developmental Cell 47/5 2020-01-24

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