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Article

Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line

  • Authors:
    • Wen-Yue Zhuang
    • Jian-Nong Cen
    • Yun Zhao
    • Zi-Xing Chen
  • View Affiliations / Copyright

    Affiliations: The First Affiliated Hospital, Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, Jiangsu, P.R. China, Cyrus Tang Hematology Center, Medical College, Soochow University, Suzhou, Jiangsu, P.R. China
  • Pages: 185-192
    |
    Published online on: May 14, 2013
       https://doi.org/10.3892/or.2013.2459
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Abstract

The AML1‑ETO fusion transcription factor generated by the t(8;21) translocation is considered to deregulate the expression of genes that are crucial for normal differentiation and proliferation of hematopoietic progenitors, resulting in acute myelogenous leukemia by recruiting co-repressor complexes to DNA. To investigate the role of AML1‑ETO in leukemogenesis, we transfected the cloned AML1‑ETO cDNA and expressed the AML1‑ETO protein in U937 myelomonocytic leukemia cells. By focusing on the anti-apoptotic gene Bcl‑2, the key regulator gene of granulocytic differentiation CCAAT/enhancer-binding protein α (CEBPA) and the tumor suppressor gene p14ARF, we found that both AML1‑ETO-expressing cell lines and t(8;21) leukemia samples displayed low levels of these three genes. Chromatin immunoprecipitation assays demonstrated that Bcl-2, CEBPA and p14ARF were direct transcriptional targets of AML1‑ETO. The universal binding of AML1‑ETO to genomic DNA resulted in recruitment of methyl-CpG binding protein 2 (MeCP2), reduction of histone H3 or H4 acetylation and increased trimethylation of histone H3 lysine 9 as well as lysine 27 indicating that AML1‑ETO induced heterochromatic silencing of Bcl-2, CEBPA and p14ARF. These results suggested that the aberrant transcription factor AML1‑ETO epigenetically silenced the function of the Bcl-2, CEBPA and p14ARF genes by inducing repressed chromatin configurations at their promoters through histone modifications.
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Copy and paste a formatted citation
Spandidos Publications style
Zhuang W, Cen J, Zhao Y and Chen Z: Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line. Oncol Rep 30: 185-192, 2013.
APA
Zhuang, W., Cen, J., Zhao, Y., & Chen, Z. (2013). Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line. Oncology Reports, 30, 185-192. https://doi.org/10.3892/or.2013.2459
MLA
Zhuang, W., Cen, J., Zhao, Y., Chen, Z."Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line". Oncology Reports 30.1 (2013): 185-192.
Chicago
Zhuang, W., Cen, J., Zhao, Y., Chen, Z."Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line". Oncology Reports 30, no. 1 (2013): 185-192. https://doi.org/10.3892/or.2013.2459
Copy and paste a formatted citation
x
Spandidos Publications style
Zhuang W, Cen J, Zhao Y and Chen Z: Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line. Oncol Rep 30: 185-192, 2013.
APA
Zhuang, W., Cen, J., Zhao, Y., & Chen, Z. (2013). Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line. Oncology Reports, 30, 185-192. https://doi.org/10.3892/or.2013.2459
MLA
Zhuang, W., Cen, J., Zhao, Y., Chen, Z."Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line". Oncology Reports 30.1 (2013): 185-192.
Chicago
Zhuang, W., Cen, J., Zhao, Y., Chen, Z."Epigenetic silencing of Bcl-2, CEBPA and p14ARF by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line". Oncology Reports 30, no. 1 (2013): 185-192. https://doi.org/10.3892/or.2013.2459
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