Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA358213 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression
| PRJNA388150 | ENA
Project description:Chondrocyte differentiation is regulated at a transcriptional level and by various hormonal stimuli. Since chondrocyte differentiation is important for normal skeletal growth, inadequate amounts of differentiation can lead to pathological conditions such as osteoarthritis. 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 shortened long bones that have morphological deformities due to impaired chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from control and Uhrf1ΔLimb/ΔLimb mice revealed that expression levels of proliferative chondrocyte marker genes were downregulated, whereas hypertrophic chondrocyte marker genes were upregulated. In addition, gene ontology analyses and Gene Set Enrichment Analysis (GSEA) suggested that limb growth retardation due to compromised chondrocyte differentiation might be caused by increased activity of the focal adhesion signaling pathway. These results indicated that Uhrf1 has a crucial role in normal skeletal maturation by coordinating transcriptional regulatory networks during chondrocyte differentiation.
2017-12-23 | GSE92641 | GEO
Project description: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.
2018-01-01 | GSE99335 | GEO
Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice.
2016-09-13 | GSE74938 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:SPO11-promoted DNA double-strand breaks (DSBs) formation is a crucial step for meiotic recombination, and it is indispensable to detect the broken DNA ends accurately for dissecting the molecular mechanisms behind. Here, we report a novel technique, named DEtail-seq (DNA End tailing followed by sequencing), that can directly and quantitatively capture the meiotic DSB 3’ overhang hotspots at single-nucleotide resolution.
2023-01-08 | GSE154289 | GEO
Project description:Transcriptional profiling of growth plate chondrocyte differentiation yields insight into endochondral ossification
| PRJNA99437 | ENA
Project description: Not available
| S-EPMC395764 | biostudies-literature
Project description: Not available
| S-EPMC4490682 | biostudies-literature
Project description: Not available
| S-EPMC5728457 | biostudies-literature