Pharmaceutical Sciences Faculty Publications

Document Type

Article

Publication Date

1-1-2012

Journal Title

PLoS One

ISSN

1932-6203

Volume

7

Issue

12

First Page

51407

Last Page

51407

DOI

10.1371/journal.pone.0051407

PubMed ID

23236496

PubMed Central® ID

PMC3517524

Abstract

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.

Keywords

Blotting, cell differentiation, cell transformation, neoplastic, DNA primers, glioblastoma, histones, immunohistochemistry, immunoprecipitation, jumonji, mass spectrometry

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