|
| Status |
Public on Jan 01, 2018 |
| Title |
Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1ΔLimb/ΔLimb) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation as well as proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1ΔLimb/ΔLimb mice demonstrates abnormal acceleration of chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq reveal that Uhrf1 deficiency cause decreased genome-wide DNA methylation status and reduction in the promoters of specific genes such as Hspb1, which affects chondrocyte differentiation. These results indicate that Uhrf1 governs cell-type specific transcriptional regulation through genome-wide DNA methylation alteration and regulates consequent cell differentiation and skeletal maturation.
|
| |
|
| Overall design |
DNA methylation profiles of primary chondrocytes obtained from Control and cKO mice were analyzed using MBD2 mediated methylated DNA enrichment followed by next generation sequencing (MBD-seq) with Illumina MiSeq.
|
| |
|
| Contributor(s) |
Imai Y, Yamashita M, Ideta-Otsuka M, Igarashi K |
| Citation(s) |
29180567 |
| Submission date |
May 26, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
KATSUHIDE IGARASHI |
| E-mail(s) |
k-igarashi@hoshi.ac.jp
|
| Phone |
+81-3-3786-1011
|
| Organization name |
Hoshi University School of Pharmacy and Pharmaceutical Science
|
| Department |
Life Science Tokyo Advanced Research center (L-StaR)
|
| Street address |
2-4-41 Ebara
|
| City |
Shinagawa-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
142-8501 |
| Country |
Japan |
| |
|
| Platforms (1) |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA388150 |
| SRA |
SRP108104 |
