PubMed Central® ID
Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.
Blotting, cell differentiation, cell transformation, neoplastic, DNA primers, glioblastoma, histones, immunohistochemistry, immunoprecipitation, jumonji, mass spectrometry
Ene, Chibawanye I.; Edwards, Lincoln; Riddick, Gregory; Baysan, Mehmet; Woolard, Kevin; Kotliarova, Svetlana; Lai, Chen; Belova, Galina; Cam, Maggie; Walling, Jennifer; Zhou, Ming; Stevenson, Holly; Kim, Hong Sug; Killian, Keith; Veenstra, Timothy; Bailey, Rolanda; Song, Hua; Zhang, Wei; and Fine, Howard A., "Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization." (2012). Pharmaceutical Sciences Faculty Publications. 206.