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| Status |
Public on Dec 31, 2014 |
| Title |
Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The pluripotent mammalian epiblast undergoes unusually fast cell proliferation. This rapid growth is expected to generate a high transcriptional demand, but the underlying mechanisms remain unknown. We report that the chromatin remodeler Chd1, which binds the activating histone mark H3K4me3 and is associated with transcription, is required for development of the mouse epiblast. Chd1-/- embryos exhibit proliferation defects and increased apoptosis, are smaller than controls by E5.5, and fail to grow, become patterned or gastrulate. We show that Chd1-/- ES cells have a self-renewal defect and a genome-wide reduction in transcriptional output that is associated with losses in RNA Pol II elongation at growth-promoting genes, including ribosomal proteins. We also report that Chd1 directly regulates ribosomal RNA transcription and that both Chd1-/- epiblast cells in vivo and ES cells in vitro express significantly lower levels of ribosomal RNA. Single cell analyses reveal abnormal nucleolar morphology in mutants in vivo and in vitro. These data indicate that Chd1 promotes a globally elevated transcriptional output required to sustain the distinct rapid growth of the mouse epiblast.
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| Overall design |
Cell-number normalized RNA-seq from wild-type and Chd1-/- mouse embryonic stem cells.
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| Contributor(s) |
Guzman-Ayala M, Sachs M, Koh FM, Onodera CS, Bulut-Karslioglu A, Lin CJ, Wong P, Nitta R, Song JS, Ramalho-Santos M |
| Citation(s) |
25480920 |
| Submission date |
May 13, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Courtney Onodera |
| E-mail(s) |
courtney.onodera@ucsf.edu
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| Organization name |
University of California, San Francisco
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| Street address |
1450 Third St, HD374
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA247363 |
| SRA |
SRP041944 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57609_set1_rnaseq_processed.txt.gz |
457.1 Kb |
(ftp)(http) |
TXT |
| GSE57609_set2_rnaseq_processed.txt.gz |
469.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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