|
| Status |
Public on Nov 13, 2020 |
| Title |
H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Heterochromatin, which is a densely packed chromatin state that is transcriptionally silent, is a critical regulator of gene expression. However, it is unclear how the repressive histone modification, H4K20me3, or the histone methyltransferase, SUV420H2, regulate embryonic stem (ES) cell fate by patterning the epigenetic landscape. Here, we report that depletion of SUV420H2 leads to a near complete loss of H4K20me3 genome-wide, dysregulated gene expression, and delayed ES cell differentiation. SUV420H2-bound regions are enriched with repetitive DNA elements, which are de-repressed in SUV420H2 knockout ES cells. Moreover, SUV420H2 regulation of H4K20me3-marked heterochromatin controls chromatin architecture, including fine-scale interactions between gene regulatory elements in pluripotent ES cells. SUV420H2 plays a critical role in stabilizing the three-dimensional (3D) chromatin landscape of ES cells, where loss of SUV420H2 results in A/B compartment switching, perturbed chromatin insulation, and altered chromatin interactions of pericentric heterochromatin, indicative of localized decondensation. In addition, depletion of SUV420H2 resulted in compromised interactions between H4K20me3 and gene regulatory regions. Together, these findings describe a novel role for SUV420H2 in regulating the chromatin landscape of ES cells.
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| |
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| Overall design |
Hi-C of wild-type and SUV420H2 knockout undifferentiated murine ES cells
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| |
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| Contributor(s) |
Kidder BL |
| Citation(s) |
33144397 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K22 HL126842 |
Regulation of chromatin and genome stability by the H4K20 methyltransferase SMYD5 |
WAYNE STATE UNIVERSITY |
Benjamin L Kidder |
|
| |
| Submission date |
May 05, 2019 |
| Last update date |
Nov 15, 2020 |
| 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) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (6)
|
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| This SubSeries is part of SuperSeries: |
| GSE130725 |
H4K20me3 methyltransferase SUV420H2 shapes the three-dimensional chromatin landscape of pluripotent embryonic stem cells |
|
| Relations |
| BioProject |
PRJNA541180 |
| SRA |
SRP195401 |
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