Dnmt1 determines bone length by regulating energy metabolism of growth plate chondrocytes [MBD-seq]
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ABSTRACT:
PROVIDER: PRJNA1127614 | ENA |
REPOSITORIES: ENA
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Project description:Chondrocytes differentiated from mesenchymal stem cells play a role in determining skeletal patterns by ossification. However, it is still unclear how the maintenance DNA methylation in chondrocytes regulates differentiation and skeletal formation. In Musculoskeletal Knowledge Portal, Dnmt1 was significantly associated with “Height”. In fact, long bone of limb specific Dnmt1 deficient mice was significantly shortened due to decreased chondrocyte proliferation and accelerated differentiation. Furthermore, integrated analysis of RNA-Seq and MBD-Seq revealed that in Dnmt1ΔPrx1 chondrocytes, reduced DNA methylation resulted in an increase in energy metabolism-related genes in addition to ossification-related genes. Metabolomic analysis confirmed that almost all energy metabolites were increased in Dnmt1ΔPrx1 chondrocytes. These results indicate that Dnmt1 mediated maintenance DNA methylation governs chondrocyte differentiation by regulating energy metabolism through both gene expression and metabolite supply. Taken together, this study suggested that appropriate DNA methylation status in chondrocytes can orchestrate growth plate mineralization and subsequently determine bone length.
2025-09-15 | GSE270641 | GEO
Project description:Chondrocytes differentiated from mesenchymal stem cells play a role in determining skeletal patterns by ossification. However, it is still unclear how the maintenance DNA methylation in chondrocytes regulates differentiation and skeletal formation. In Musculoskeletal Knowledge Portal, Dnmt1 was significantly associated with “Height”. In fact, long bone of limb specific Dnmt1 deficient mice was significantly shortened due to decreased chondrocyte proliferation and accelerated differentiation. Furthermore, integrated analysis of RNA-Seq and MBD-Seq revealed that in Dnmt1ΔPrx1 chondrocytes, reduced DNA methylation resulted in an increase in energy metabolism-related genes in addition to ossification-related genes. Metabolomic analysis confirmed that almost all energy metabolites were increased in Dnmt1ΔPrx1 chondrocytes. These results indicate that Dnmt1 mediated maintenance DNA methylation governs chondrocyte differentiation by regulating energy metabolism through both gene expression and metabolite supply. Taken together, this study suggested that appropriate DNA methylation status in chondrocytes can orchestrate growth plate mineralization and subsequently determine bone length.
2025-09-15 | GSE270640 | GEO
Project description:Dnmt1 determines bone length by regulating energy metabolism of growth plate chondrocytes [RNA-seq]
| PRJNA1127613 | ENA
Project description:Growth plate chondrocytes were isolated from the distal metacarpus of young dairy cattle (all under 10 mo of age), the chondrocytes were released from the extracellular matrix by digestion with Collagenase P for 4 hours, and the various zones of the growth plate were separated by density centrifugation. The least-dense Hypertrophic Zone (HZ) cells were compared to the most-dense Reserve Zone (RZ) cells. 6 pairs of HZ vs RZ were compared by microarray.
2009-10-27 | GSE18738 | GEO
Project description:Growth plate chondrocytes were isolated from the distal metacarpus of young dairy cattle (all under 10 mo of age), the chondrocytes were released from the extracellular matrix by digestion with Collagenase P for 4 hours, and the various zones of the growth plate were separated by density centrifugation. The least-dense Hypertrophic Zone (HZ) cells were compared to the most-dense Reserve Zone (RZ) cells. 6 pairs of HZ vs RZ were compared by microarray. Experiment Overall Design: Growth plate chondrocytes were isolated from the distal metacarpus of young dairy cattle (all under 10 mo of age), the chondrocytes were released from the extracellular matrix by digestion with Collagenase P for 4 hours, and the various zones of the growth plate were separated by density centrifugation. The least-dense Hypertrophic Zone (HZ) cells were compared to the most-dense Reserve Zone (RZ) cells. Six independent sample pairs of HZ vs RZ were compared by microarray.
2009-10-30 | E-GEOD-18738 | biostudies-arrayexpress
Project description:We set out to reveal single cell transcriptional profiles of neonatal growth plate chondrocytes
2019-01-23 | GSE125464 | GEO
Project description:Proliferative zone chondrocytes were microdissected from control and Ift88-deleted growth plates to determine gene expression profiles regulated by primary cilia. Four total samples were analyzed. Two biological replicates of proliferative zone chondrocytes microdissected from control mice and two biological replicates from Ift88 deleted (Col2aCre;Ift88fl/fl) mice. Control and experimental mice were in the Bl/6 background.
2013-01-02 | E-GEOD-35003 | biostudies-arrayexpress
Project description:Gowth plate chondrocytes include heterogenous cell population and cellular diversity of these chondrocytes remains to be elucidated. We used single cell RNA sequencing to uncover the diverssity of growth plate chondrocytes and identify noel marker genes selectively expressed in pre-hypertrophic chondrocytes.
2024-11-21 | GSE271634 | GEO
Project description:In order to gain insight into DNA methylation readout, we have established a controlled strategy for profiling genomic targeting of chromatin-interacting factors in vivo. With this approach we determined binding preferences for the methyl-CpG binding domain (MBD) family of proteins, including disease relevant mutants, deletions and isoforms. In vivo binding of MBD proteins occurs as a linear function of local methylation density, and is dependent on functional MBD domain M-bM-^@M-^S methyl-CpG interactions. This directs specificity of MBD proteins to methylated, CpG dense and inactive regulatory regions. In contrast, binding to unmethylated sites is MBD protein specific and mediated via alternative domains or protein-protein interactions. The latter is observed for NuRD complex-mediated MBD2 tethering to a subset of unmethylated, tissue-specific regulatory regions, similar to MBD3. These functional binding maps reveal methylation-dependent and -independent binding modes determined by distinct protein domains and revise current models of DNA methylation readout through MBD proteins. Comparative binding analysis for the MBD family of proteins utilizing recombinase-assisted mapping of biotin-tagged proteins (RAMBiO). This set contains maps for 29 samples including wild type MBD proteins, mutants and domain variants in mouse ES cells, derived neurons (NP and TN) and Dnmt1/3a/3b triple-KO ES cells (TKO).
2013-04-01 | E-GEOD-39610 | biostudies-arrayexpress
Project description:Genome-wide passive DNA demethylation in cleavage-stage mouse embryos is related to the cytoplasmic localization of the maintenance methyltransferase DNMT1. However, recent studies provided evidence of the nuclear localization of DNMT1 and its contribution to the maintenance of methylation levels of imprinted regions and other genomic loci in early embryos. Using the DNA-adenine methylase identification (DamID) method, we identified Dnmt1-binding regions in 4-cell and 8-cell embryos. The unbiased distribution of Dnmt1 peaks in the genic regions (promoters and CpG islands) as well as the absence of a correlation between the Dnmt1 peaks and the expression levels of the peak-associated genes refute the active participation of Dnmt1 in the transcriptional regulation of genes in the early developmental period. Instead, Dnmt1 was found to associate with genomic retroelements in a greatly biased fashion, particularly with the long interspersed nuclear elements (LINE1) and endogenous retrovirus type-K (ERVK) sequences. Transcriptomic analysis revealed that the transcripts of the Dnmt1-enriched retroelements were overrepresented in Dnmt1 knockdown embryos. Finally, methyl-CpG-binding-domain sequencing proved that the Dnmt1-enriched retroelements, which were densely methylated in wild-type embryos, became demethylated in the Dnmt1-depleted embryos. Our results indicate that Dnmt1 is involved in the repression of retroelements through DNA methylation in early mouse development.
2020-07-19 | GSE150463 | GEO