Back to Search
Start Over
Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation.
Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation.
- Source :
-
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2016 Mar; Vol. 31 (3), pp. 524-34. Date of Electronic Publication: 2015 Oct 05. - Publication Year :
- 2016
-
Abstract
- Regulation of gene expression changes during chondrogenic differentiation by DNA methylation and demethylation is little understood. Methylated cytosines (5mC) are oxidized by the ten-eleven-translocation (TET) proteins to 5-hydroxymethylcytosines (5hmC), 5-formylcytosines (5fC), and 5-carboxylcytosines (5caC), eventually leading to a replacement by unmethylated cytosines (C), ie, DNA demethylation. Additionally, 5hmC is stable and acts as an epigenetic mark by itself. Here, we report that global changes in 5hmC mark chondrogenic differentiation in vivo and in vitro. Tibia anlagen and growth plate analyses during limb development at mouse embryonic days E 11.5, 13.5, and 17.5 showed dynamic changes in 5hmC levels in the differentiating chondrocytes. A similar increase in 5hmC levels was observed in the ATDC5 chondroprogenitor cell line accompanied by increased expression of the TET proteins during in vitro differentiation. Loss of TET1 in ATDC5 decreased 5hmC levels and impaired differentiation, demonstrating a functional role for TET1-mediated 5hmC dynamics in chondrogenic differentiation. Global analyses of the 5hmC-enriched sequences during early and late chondrogenic differentiation identified 5hmC distribution to be enriched in the regulatory regions of genes preceding the transcription start site (TSS), as well as in the gene bodies. Stable gains in 5hmC were observed in specific subsets of genes, including genes associated with cartilage development and in chondrogenic lineage-specific genes. 5hmC gains in regulatory promoter and enhancer regions as well as in gene bodies were strongly associated with activated but not repressed genes, indicating a potential regulatory role for DNA hydroxymethylation in chondrogenic gene expression.<br /> (© 2015 American Society for Bone and Mineral Research.)
- Subjects :
- 5-Methylcytosine analogs & derivatives
Animals
Cartilage embryology
Chondrocytes cytology
Chondrocytes metabolism
Cytosine metabolism
DNA, Intergenic genetics
DNA-Binding Proteins metabolism
Embryonic Development genetics
Extremities embryology
Gene Expression Regulation, Developmental
Mice
Proto-Oncogene Proteins metabolism
Stem Cells cytology
Cell Differentiation genetics
Chondrogenesis genetics
Cytosine analogs & derivatives
Transcriptional Activation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1523-4681
- Volume :
- 31
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
- Publication Type :
- Academic Journal
- Accession number :
- 26363184
- Full Text :
- https://doi.org/10.1002/jbmr.2711