Transcriptomics

Dataset Information

35

Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma (methylation)


ABSTRACT: Therapeutic targeting of the Wnt pathway is of high clinical interest for treating bone loss disorders such as osteoporosis. These therapies inhibit the action of negative regulators of osteoblastic Wnt signaling. The observation that Wnt inhibitory factor 1 (WNT1) was epigenetic silencing in osteosarcoma (OS) raised concerns for such a treatment approach. In this study, genome-wide methylation profiling of OS derived from mouse models demonstrated Wif1 silencing in OS is not driven by DNA methylation. Treatment of mouse and human OS cells with methylation and HDAC inhibitors showed Wif1 was unresponsive to methylation inhibition but responded robustly to HDAC inhibition. Consistent with an HDAC dependent mechanism of silencing, the Wif1 locus in OS was characterized by low levels of acetylation and a bivalent H3K4/H3K27 trimethylation state. Wif1 expression marked late stages of normal osteoblast development and stratified OS tumours based on differentiation stage across species. Culture of human and mouse OS cells under differentiation inductive conditions increased expression of Wif1 in parallel with known osteoblast differentiation markers. Together these results demonstrate that Wif1 is not targeted for silencing by DNA methylation in OS. The reduced expression of Wif1 in OS cells is in context with their stage in differentiation. 3 cell lines derived from primary tumors from p53 Rb Osterix-Cre:lox OS model, 3 Osteoblasts (differentiated Kusa4b10 cells (21 days under osteoblastic differentiation conditions)

ORGANISM(S): Mus musculus  

SUBMITTER: S Bhattacharya  S R Taylor   A C Green   L E Purton   A M Chalk   M D Robinson   T J Martin   A Gupte   E K Baker   Alistair Morgan Chalk   C R Walkley    

PROVIDER: E-GEOD-47571 | ArrayExpress | 2015-08-19

SECONDARY ACCESSION(S): GSE47571PRJNA206096

REPOSITORIES: GEO, ArrayExpress

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