|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Jan 18, 2017 |
Title |
Jmjd2c/Kdm4c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
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.
|
|
|
Overall design |
Flag ChIP was performed for identification of Flag-Jmjd2c binding sites in mouse ES cells cultured in either naïve (2i/LIF) or primed (serum/LIF) conditions.
|
|
|
Contributor(s) |
Tomaz RA, Harman JL, Karimlou D, Weavers L, Fritsch L, Bou-Kheir T, Bell E, del Valle Torres I, Niakan KK, Fisher C, Joshi O, Stunnenberg HG, Curry E, Ait-Si-Ali S, Jørgensen HF, Azuara V |
Citation(s) |
28087629 |
Submission date |
Jan 17, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Rute A. Tomaz |
E-mail(s) |
r.tomaz11@imperial.ac.uk
|
Organization name |
Imperial College London
|
Street address |
IRDB, Imperial College, Hammersmith Campus, Du Cane Road
|
City |
London |
State/province |
London |
ZIP/Postal code |
W12 0NN |
Country |
United Kingdom |
|
|
Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
Samples (7)
|
|
Relations |
BioProject |
PRJNA362204 |
SRA |
SRP096899 |
Supplementary file |
Size |
Download |
File type/resource |
GSE93721_RAW.tar |
850.5 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
|