Imperial College London
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DrMichellePercharde

Faculty of Medicine, Institute of Clinical Sciences

Honorary Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 8299m.percharde Website

 
 
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Location

 

CRB 2006 / 2013Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Xie:2021:10.1101/2021.11.11.468235,
author = {Xie, SQ and Leeke, BJ and Whidling, C and Wagner, RT and Garcia-Llagostera, F and Chammas, P and Cheung, NT-F and Dormann, D and McManus, MT and Percharde, M},
doi = {10.1101/2021.11.11.468235},
title = {Nucleolar-based <i>Dux</i> repression is essential for 2-cell stage exit},
url = {http://dx.doi.org/10.1101/2021.11.11.468235},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>Upon fertilisation, the mammalian embryo must switch from dependence on maternal transcripts to transcribing its own genome, and in mice involves the transient upregulation of MERVL transposons and MERVL-driven genes at the 2-cell stage. The mechanisms and requirement for MERVL and 2-cell (2C) gene upregulation are poorly understood. Moreover, this MERVL-driven transcriptional program must be rapidly shut off to allow 2C exit and developmental progression. Here, we report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. 2C-like cells and 2C embryos show similar immature nucleoli with altered structure and reduced rRNA output. We reveal that nucleolar disruption via blocking Pol I activity or preventing nucleolar phase separation enhances conversion to a 2C-like state in embryonic stem cells (ESCs) by detachment of the MERVL activator <jats:italic>Dux</jats:italic> from the nucleolar surface. In embryos, nucleolar disruption prevents proper <jats:italic>Dux</jats:italic> silencing and leads to 2-4 cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation and gene repression during early development.</jats:p>
AU  - Xie,SQ
AU  - Leeke,BJ
AU  - Whidling,C
AU  - Wagner,RT
AU  - Garcia-Llagostera,F
AU  - Chammas,P
AU  - Cheung,NT-F
AU  - Dormann,D
AU  - McManus,MT
AU  - Percharde,M
DO  - 10.1101/2021.11.11.468235
PY  - 2021///
TI  - Nucleolar-based <i>Dux</i> repression is essential for 2-cell stage exit
UR  - http://dx.doi.org/10.1101/2021.11.11.468235
ER  -
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