Imperial College London
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DrEdCurry

Faculty of Medicine, Department of Surgery & Cancer

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 5943e.curry

 
 
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Location

 

Open PlanInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tomaz:2017:10.1242/dev.142489,
author = {Tomaz, RA and Harman, JL and Karimlou, D and Weavers, L and Fritsch, L and Bou-Kheir, T and Bell, E and del, Valle Torres I and Niakan, KK and Fisher, C and Joshi, O and Stunnenberg, HG and Curry, E and Ait-Si-Ali, S and Jorgensen, HF and Azuara, V},
doi = {10.1242/dev.142489},
journal = {Development},
pages = {567--579},
title = {Jmjd2c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation},
url = {http://dx.doi.org/10.1242/dev.142489},
volume = {144},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Jmjd2/Kdm4 H3K9-demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we uncover that Jmjd2c facilitates this process by stabilizing the assembly of Mediator-Cohesin complexes at lineage-specific enhancers. Functionally, we show that Jmjd2c is required in ESCs to initiate appropriate gene expression programs upon somatic multi-lineage differentiation. In the absence of Jmjd2c, differentiation is stalled at an early post-implantation epiblast-like stage, while Jmjd2c-knockout ESCs remain capable of forming extra-embryonic endoderm derivatives. Dissection of the underlying molecular basis revealed that Jmjd2c is re-distributed to lineage-specific enhancers during ESC priming for differentiation. Interestingly, Jmjd2c-bound enhancers are co-occupied by the H3K9-methyltransferase G9a/Ehmt2, independently of its H3K9-modifying activity. Loss of Jmjd2c abrogates G9a recruitment and furthermore destabilizes loading of the Mediator and Cohesin components Med1 and Smc1a at newly activated and poised enhancers in ESC-derived epiblast-like cells. These findings unveil Jmjd2c-G9a as novel enhancer-associated factors, and implicate Jmjd2c as a molecular scaffold for the assembly of essential enhancer-protein complexes with impact on timely gene activation.
AU  - Tomaz,RA
AU  - Harman,JL
AU  - Karimlou,D
AU  - Weavers,L
AU  - Fritsch,L
AU  - Bou-Kheir,T
AU  - Bell,E
AU  - del,Valle Torres I
AU  - Niakan,KK
AU  - Fisher,C
AU  - Joshi,O
AU  - Stunnenberg,HG
AU  - Curry,E
AU  - Ait-Si-Ali,S
AU  - Jorgensen,HF
AU  - Azuara,V
DO  - 10.1242/dev.142489
EP  - 579
PY  - 2017///
SN  - 0950-1991
SP  - 567
TI  - Jmjd2c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation
T2  - Development
UR  - http://dx.doi.org/10.1242/dev.142489
UR  - http://hdl.handle.net/10044/1/43506
VL  - 144
ER  -
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