|
| Status |
Public on Jun 12, 2017 |
| Title |
SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated histone lysine 20 (H4K20me3) in pluripotency and development are largely unknown. Here, we show that the histone lysine methyltransferase SMYD5 mediates H4K20me3 at heterochromatin regions. Depletion of SMYD5 leads to compromised self-renewal, including dysregulated expression of OCT4 targets, and perturbed differentiation. SMYD5 bound regions are enriched with repetitive DNA elements. Knockdown of SMYD5 results in a global decrease of H4K20me3 levels, a redistribution of heterochromatin constituents including H3K9me3/2, G9a, and HP1α, and de-repression of endogenous retroelements. A loss of SMYD5-dependent silencing of heterochromatin nearby genic regions leads to upregulated expression of lineage-specific genes, thus contributing to the decreased self-renewal and accelerated differentiation of SMYD5-depeleted ES cells. Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin.
|
| |
|
| Overall design |
RNA-Seq of undifferentiated and differentiated murine shLuc and shSmyd5 ES cells
|
| |
|
| Contributor(s) |
Kidder BL, Zhao K |
| Citation(s) |
28250819 |
| |
| Submission date |
Jan 26, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Benjamin L Kidder |
| E-mail(s) |
benjamin.kidder@wayne.edu
|
| Organization name |
Wayne State University
|
| Department |
Oncology
|
| Lab |
Laboratory of Epigenomics
|
| Street address |
4100 John R St
|
| City |
Detroit |
| State/province |
MI |
| ZIP/Postal code |
48201 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (10)
|
|
| This SubSeries is part of SuperSeries: |
| GSE94086 |
SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation |
|
| Relations |
| BioProject |
PRJNA368814 |
| SRA |
SRP097856 |
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