Regulation of the JMJD3 (KDM6B) histone demethylase in glioblastoma stem cells by STAT3

PloS One
Maureen M Sherry-LynesBrent H Cochran

Abstract

The growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect. Consistent with this observation, STAT3 inhibition leads to histone H3K27 demethylation of neural differentiation genes, such as Myt1, FGF21, and GDF15. These results demonstrate that the regulation of Jmjd3 by STAT3 maintains repression of differentiation specific genes and is therefore important for the maintenance of self-renewal of normal neural and glioblastoma stem cells.

Citations

Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·D S OryR C Mulligan
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 3, 2004·Genes & Development·Antonis KirmizisPeggy J Farnham
Mar 1, 2005·Oncogene·Daniel J DauerEric B Haura
Mar 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hui SongJiayuh Lin
Jun 7, 2005·Journal of Neurochemistry·Elena RommLynn D Hudson
Jun 7, 2005·Nature Medicine·James E Darnell
Jun 11, 2005·Journal of Neuroscience Research·Feng GuMasahiro Sakanaka
Jun 27, 2006·Nature·Andreas Androutsellis-TheotokisRonald D G McKay
Aug 22, 2006·Current Biology : CB·Maria A FriasDavid M Sabatini
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Khandaker SiddiqueeJames Turkson
Oct 10, 2007·Cell Research·Yang XiangCharlie Degui Chen
Feb 21, 2008·Molecular and Cellular Biology·Kavitha SarmaDanny Reinberg
Dec 17, 2008·PloS One·Benjamin L KidderStephen Palmer
Mar 31, 2009·Nature Genetics·Gijs van HaaftenP Andrew Futreal
Jul 17, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mohamed AbdouhGilbert Bernier
Nov 26, 2009·Cancer Research·Mario-Luca SuvàIvan Stamenkovic
Dec 4, 2009·Current Protocols in Bioinformatics·Donna KarolchikW James Kent
Dec 25, 2009·Nature·Maria Stella CarroAntonio Iavarone
Sep 2, 2010·Cell Stem Cell·Jian YangAustin Smith
Dec 7, 2010·Nucleic Acids Research·Daniel HebenstreitSarah A Teichmann
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ian MazeEric J Nestler

Related Concepts

Arsa
Glioblastoma Multiforme
Embryo
Real-Time Polymerase Chain Reaction
KDM6B protein, human
Gene Expression Regulation, Neoplastic
Subfamily lentivirinae
DNA Methylation [PE]
Histone antigen
Dimethyl Sulfoxide

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.