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.
| Original language | English (US) |
|---|---|
| Article number | e51407 |
| Journal | PLoS One |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 7 2012 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization. / Ene, Chibawanye I.; Edwards, Lincoln; Riddick, Gregory; Baysan, Mehmet; Woolard, Kevin D; 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; Fine, Howard A.
In: PLoS One, Vol. 7, No. 12, e51407, 07.12.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization
AU - Ene, Chibawanye I.
AU - Edwards, Lincoln
AU - Riddick, Gregory
AU - Baysan, Mehmet
AU - Woolard, Kevin D
AU - Kotliarova, Svetlana
AU - Lai, Chen
AU - Belova, Galina
AU - Cam, Maggie
AU - Walling, Jennifer
AU - Zhou, Ming
AU - Stevenson, Holly
AU - Kim, Hong Sug
AU - Killian, Keith
AU - Veenstra, Timothy
AU - Bailey, Rolanda
AU - Song, Hua
AU - Zhang, Wei
AU - Fine, Howard A.
PY - 2012/12/7
Y1 - 2012/12/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870874138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870874138&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0051407
DO - 10.1371/journal.pone.0051407
M3 - Article
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 12
M1 - e51407
ER -