Project description:The Ten-eleven translocation (TET) family of dioxygenases can mediate cytosine demethylation by catalyzing the oxidation of 5-methylcytosine (5mC). TET-mediated DNA demethylation controls the proper differentiation of embryonic stem cells and TET proteins display functional redundancy during early gastrulation. However, it is unclear if TET proteins have functional significance in mammalian skeletal development. Here, we report that Tet deficiency in mesoderm mesenchymal stem cells results in severe defects of bone development. The existence of any single Tet gene allele can support early bone formation, suggesting a potential functional redundancy of TET proteins. Integrative analyses of RNA-seq, Whole Genome Bisulfite Sequencing (WGBS) and Assay for Transposase-Accessible Chromatin (ATAC-seq) demonstrate that TET-mediated demethylation increases the chromatin accessibility of target genes by RUNX2 and facilities RUNX2-regulated transcription. In addition, TET proteins interact with RUNX2 through their catalytic domain to regulate cytosine methylation around RUNX2 binding region. The catalytic domain is indispensable for TET proteins to regulate RUNX2 transcription activity on its target genes and to regulate bone development. These results demonstrate that TET proteins function redundantly to regulate RUNX2 activity via dual mechanisms and maintain skeletal homeostasis.
Project description:RNAseq was performed by to compare gene expression between wildtype and Smchd1 KO ES cells, the gene expression pattern in Dux KO mutants , Double KO mutant Tet-TKO mutants and Tet TKO plus SMCKHD1 KO mutants were analyzed by RNAseq.
Project description:This study is to analyze the transcriptomic profiles of Plp-CreERT2;QKLoxP/LoxP (Qk-KO) and Plp-CreERT2;QKLoxP/+ (WT) mice and WT and Qk-KO oligodendrocytes to determine the differentially expressed genes.
Project description:This study compares cardiac induction time-courses using (i) wild-type hESCs subjected to a standard directed differentiation protocol, (ii) EOMES knockout hESCs subjected to the same protocol, and (iii) EOMES KO / TET-ON hESCs subjected to a TET-ON protocol.
Project description:This study is to analyze the transcriptomic profiles of 6 weeks 0.2% cuprizone treated Cx3cr1-CreER;QKLoxP/LoxP (Qk-KO) and Cx3cr1-CreER;QK LoxP/+ (WT) mice
Project description:To examine whether energy starvation caused by the increase in rRNA transcription affects liver metabolism, we compared the gene expression profiles of WT and NML-KO livers using Affymetrix microarray technology. We analyzed 5 livers of WT mice and 5 livers of NML-KO mice.
Project description:To examine whether energy starvation caused by the increase in rRNA transcription affects liver metabolism, we compared the gene expression profiles of WT and NML-KO livers using Affymetrix microarray technology.