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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on the storage and integration of epigenetic drug datasets that were obtained from laboratory experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2

Drug Name:GSK126
Drug Category:HMTi
Sample Type:human adipose-derived mesenchymal (AMSCs)?
Condition:adipose-derived mesenchymal (AMSCs)?
Experiment Type:Expression profiling by high throughput sequencing
Experiment Platform:GPL11154 Illumina HiSeq 2000 (Homo sapiens);GPL13112 Illumina HiSeq 2000 (Mus musculus)
Description:Epigenetic control of gene expression is critical for normal fetal development. However, chromatin-related mechanisms that activate bone-specific programs during osteogenesis have remained underexplored. Therefore, we investigated the expression profiles of a large cohort of epigenetic regulators (>300) during osteogenic differentiation of human mesenchymal cells derived from the stromal vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated during osteoblastic differentiation of AMSCs. Chemical inhibitor and siRNA knockdown studies show that EZH2, a histone methyltransferase that catalyzes trimethylation of histone 3 lysine 27 (H3K27me3), suppresses osteogenic differentiation. Blocking EZH2 activity promotes osteoblast differentiation and suppresses adipogenic differentiation of AMSCs. High throughput RNA sequence (mRNASeq) analysis reveals that EZH2 inhibition stimulates cell cycle inhibitory proteins and enhances the production of extracellular matrix proteins. Conditional genetic loss of Ezh2 in uncommitted mesenchymal cells (Prrx1-Cre) results in multiple defects in skeletal patterning and bone formation, including shortened forelimbs, craniosynostosis, and clinodactyly. Histological analysis and mRNASeq profiling suggest that these effects are attributable to growth plate abnormalities and premature cranial suture closure because of precocious maturation of osteoblasts. We conclude that the epigenetic activity of EZH2 is required for skeletal patterning and development, but EZH2 expression declines during terminal osteoblast differentiation and matrix production.
PubmedID:26424790
Citation:Dudakovic A;Camilleri ET; Xu F; Riester SM1;McGee-Lawrence ME; Bradley EW;Paradise CR;Lewallen EA;Thaler R;Deyle DR; Larson AN; Lewallen DG;Dietz AB;Stein GS; Montecino MA;Westendorf JJ;van Wijnen AJ.Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2. J Biol Chem2015 Nov 13;290(46):27604-17.
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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on integrating epigenetic drug studies based Omics data from high through experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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©2016 Group of Computational Epigenomics and Bioinformatics, College of Life Science, Jilin Normal University, China

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