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Molecular and Cellular Biochemistry

, Volume 394, Issue 1–2, pp 23–30 | Cite as

Histone methyltransferase G9a and H3K9 dimethylation inhibit the self-renewal of glioma cancer stem cells

  • Hong Tao
  • Haiying Li
  • Yanhuang Su
  • Danni Feng
  • Xilong Wang
  • Chun Zhang
  • Hui Ma
  • Qikuan HuEmail author
Article

Abstract

Epigenetic modification is crucial to keep the self-renewal and the “stemness” states of stem cells, not letting them to differentiate. The actual roles of Histone 3 Lysine 9 dimethylation (H3K9me2) and its methyltransferase G9a in this process are still unclear, especially in cancer stem cells. In our study, we found an interesting observation that most CD133-positive cells were H3K9me2 negative, both in glioma tissues and in cultured cells, although most cancer cells were detected to be H3K9me2 immunopositive. This implied that the G9a-dependent H3K9me2 was one of the crucial barriers of cancer stem cell self-renewal. To test the hypothesis, we examined the loss-of-function and gain-of-function of G9a. We found that bix01294, the selective inhibitor of G9a, can stimulate the sphere formation rate of glioma cancer stem cells, together with increasing Sox2 and CD133 expressions. The increase of CD133-active stem cells was confirmed by flow cytometry. On the other aspect, overexpression of G9a increased the H3K9me2 and decreased the sphere formation rate as well as the CD133 and Sox2 expressions. Since H3K9me2 modification is the major repressive switch, we predict that the repressive H3K9me2 modification may happen at the CD133 promoter regions. By chromatin precipitation assay, we confirmed that the CD133 and Sox2 promoter regions were modified by the H3K9me2. Therefore, we concluded that the G9a-dependent H3K9me2 repression on CD133 and Sox2 was one of the main switches of the self-renewal in glioma cancer stem cells.

Keywords

Cancer stem cells H3K9me2 G9a Self-renewal 

Notes

Acknowledgments

This work was supported by grants from the Chinese National 973 Projects (2011CB512115) and (2012CB722408) to Tao Sun, and grants from the National Natural Science Foundation of China to Qikuan Hu (30960150 and 31260246).

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

11010_2014_2077_MOESM1_ESM.doc (9.3 mb)
Supplementary material 1 (doc 9550 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hong Tao
    • 1
  • Haiying Li
    • 2
  • Yanhuang Su
    • 1
  • Danni Feng
    • 1
  • Xilong Wang
    • 3
  • Chun Zhang
    • 4
  • Hui Ma
    • 3
  • Qikuan Hu
    • 4
    • 1
    Email author
  1. 1.Department of PhysiologyNingxia Medical UniversityYinchuanChina
  2. 2.Inner Mongolia Wulanchabu Medical CollegeJining DistrictChina
  3. 3.General Hospital of Ningxia Medical UniversityYinchuanChina
  4. 4.Ningxia Key Lab of Cerebrocranial DiseasesThe Incubation Base of National Key LaboratoryYinchuanChina

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