Imperial College London

ProfessorBorisLenhard

Faculty of MedicineInstitute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 3313 8353b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

230ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hill:2018:10.1038/nature25964,
author = {Hill, PWS and Leitch, HG and Requena, CE and Sun, Z and Amouroux, R and Roman-Trufero, M and Borkowska, M and Terragni, J and Vaisvila, R and Linnett, S and Bagci, H and Dharmalingham, G and Haberle, V and Lenhard, B and Zheng, Y and Pradhan, S and Hajkova, P},
doi = {10.1038/nature25964},
journal = {Nature},
pages = {392--396},
title = {Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte},
url = {http://dx.doi.org/10.1038/nature25964},
volume = {555},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs)1. Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5–E11.52,3,4,5,6,7,8,9,10,11, including genome-wide loss of 5-methylcytosine2,3,4,5,7,8,9,10,11. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro12,13,14. Here we show, using an integrative approach, that this complex reprogramming process involves coordinated interplay among promoter sequence characteristics, DNA (de)methylation, the polycomb (PRC1) complex and both DNA demethylation-dependent and -independent functions of TET1 to enable the activation of a critical set of germline reprogramming-responsive genes involved in gamete generation and meiosis. Our results also reveal an unexpected role for TET1 in maintaining but not driving DNA demethylation in gonadal PGCs. Collectively, our work uncovers a fundamental biological role for gonadal germline reprogramming and identifies the epigenetic principles of the PGC-to-gonocyte transition that will help to guide attempts to recapitulate complete gametogenesis in vitro.
AU - Hill,PWS
AU - Leitch,HG
AU - Requena,CE
AU - Sun,Z
AU - Amouroux,R
AU - Roman-Trufero,M
AU - Borkowska,M
AU - Terragni,J
AU - Vaisvila,R
AU - Linnett,S
AU - Bagci,H
AU - Dharmalingham,G
AU - Haberle,V
AU - Lenhard,B
AU - Zheng,Y
AU - Pradhan,S
AU - Hajkova,P
DO - 10.1038/nature25964
EP - 396
PY - 2018///
SN - 0028-0836
SP - 392
TI - Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte
T2 - Nature
UR - http://dx.doi.org/10.1038/nature25964
UR - http://hdl.handle.net/10044/1/57599
VL - 555
ER -