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| Status |
Public on Feb 06, 2020 |
| Title |
DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [LSD1 ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mouse embryonic stem cells (ESCs) sporadically express preimplantation two-cell-stage (2C) transcripts, including MERVL endogenous retrovirus and Zscan4 cluster genes. Such 2C-like cells (2CLCs) can contribute to both embryonic and extraembryonic tissues when reintroduced into early embryos. We examined global nucleosome occupancy and gene expression in 2CLCs and identified miR-344 as the noncoding molecule that positively controls 2CLC potency. We found that activation of endogenous MERVL or miR-344-2 alone is sufficient to induce 2CLCs with induction of 2C genes and an expanded potency. Mechanistically, miR-344 is activated by the 2C-state driver DUX and post-transcriptionally represses ZMYM2 and LSD1, which recruit the HDAC corepressor to MERVL LTR for transcriptional repression. Consistently, zygotic depletion of Zmym2 compromises the totipotency-to-pluripotency transition during early development. Our studies establish the novel DUXmiR-344--|Zmym2/LsdSD1 axis that controls MERVL for expanded stem cell potency.
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| |
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| Overall design |
Genome binding/occupancy profiling of Zmym2 was performed in ESCs by ChIP sequencing.
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| |
|
| Contributor(s) |
Huang X, Wang J |
| Citation(s) |
32032525 |
| |
| Submission date |
Dec 18, 2019 |
| Last update date |
Mar 19, 2020 |
| Contact name |
Jianlong Wang |
| Organization name |
Columbia University Irving Medical Center
|
| Department |
Department of Medicine
|
| Lab |
Jianlong Wang
|
| Street address |
650 W. 168th St.
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10032 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE119820 |
DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state |
|
| Relations |
| BioProject |
PRJNA596458 |
| SRA |
SRP238091 |
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