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Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation.

Publication ,  Journal Article
Zhou, J; Huang, S; Wang, Z; Huang, J; Xu, L; Tang, X; Wan, YY; Li, Q-J; Symonds, ALJ; Long, H; Zhu, B
Published in: Nat Commun
June 3, 2019

Enhancer of zeste homolog 2 (EZH2)-mediated trimethylation of histone 3 lysine 27 (H3K27Me3) is critical for immune regulation. However, evidence is lacking to address the effect of EZH2 enzyme's activity on intestinal immune responses during inflammatory bowel disease (IBD). Here we report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In addition, we identified an increased number of functional MDSCs in the colons, which are essential for EZH2 inhibitor activity. Moreover, inhibition of EZH2 activity promotes the generation of MDSCs from hematopoietic progenitor cells in vitro, demonstrating a previously unappreciated role for EZH2 in the development of MDSCs. Together, these findings suggest the feasibility of EZH2 inhibitor clinical trials for the control of IBD. In addition, this study identifies MDSC-promoting effects of EZH2 inhibitors that may be undesirable in other therapeutic contexts and should be addressed in a clinical trial setting.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 3, 2019

Volume

10

Issue

1

Start / End Page

2427

Location

England

Related Subject Headings

  • Pyridones
  • Myeloid-Derived Suppressor Cells
  • Mice
  • Methylation
  • Inflammatory Bowel Diseases
  • Indoles
  • Indazoles
  • In Vitro Techniques
  • Histones
  • Histone Code
 

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Zhou, J., Huang, S., Wang, Z., Huang, J., Xu, L., Tang, X., … Zhu, B. (2019). Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation. Nat Commun, 10(1), 2427. https://doi.org/10.1038/s41467-019-10176-2
Zhou, Jie, Shuo Huang, Zhongyu Wang, Jiani Huang, Liang Xu, Xuefeng Tang, Yisong Y. Wan, et al. “Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation.Nat Commun 10, no. 1 (June 3, 2019): 2427. https://doi.org/10.1038/s41467-019-10176-2.
Zhou J, Huang S, Wang Z, Huang J, Xu L, Tang X, et al. Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation. Nat Commun. 2019 Jun 3;10(1):2427.
Zhou, Jie, et al. “Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation.Nat Commun, vol. 10, no. 1, June 2019, p. 2427. Pubmed, doi:10.1038/s41467-019-10176-2.
Zhou J, Huang S, Wang Z, Huang J, Xu L, Tang X, Wan YY, Li Q-J, Symonds ALJ, Long H, Zhu B. Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation. Nat Commun. 2019 Jun 3;10(1):2427.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 3, 2019

Volume

10

Issue

1

Start / End Page

2427

Location

England

Related Subject Headings

  • Pyridones
  • Myeloid-Derived Suppressor Cells
  • Mice
  • Methylation
  • Inflammatory Bowel Diseases
  • Indoles
  • Indazoles
  • In Vitro Techniques
  • Histones
  • Histone Code