BMI1 reprogrammes histone acetylation and enhances c-fos pathway via directly binding to Zmym3 in malignant myeloid progression
Article first published online: 27 FEB 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 6, pages 1004–1017, June 2014
How to Cite
Shen, H., Chen, Z., Ding, X., Qi, X., Cen, J., Wang, Y., Yao, L. and Chen, Y. (2014), BMI1 reprogrammes histone acetylation and enhances c-fos pathway via directly binding to Zmym3 in malignant myeloid progression. Journal of Cellular and Molecular Medicine, 18: 1004–1017. doi: 10.1111/jcmm.12246
- Issue published online: 24 JUL 2014
- Article first published online: 27 FEB 2014
- Manuscript Accepted: 8 JAN 2014
- Manuscript Received: 28 JUL 2013
- National Key Scientific Project of China. Grant Number: 2011CB933501
- National Natural Science Foundation of China. Grant Numbers: 81070402, 81170468
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Jiangsu Natural Science Foundation of China. Grant Number: BK2011266
- Jiangsu Provience's Key Medical Center. Grant Number: ZX201102
- Science and Technology Foundation of Suzhou Municipal Government. Grant Number: SZS201001
- myelodysplastic syndrome;
- chronic myeloid leukaemia;
The polycomb group BMI1 is proved to be crucial in malignant myeloid progression. However, the underlying mechanism of the action of BMI1 in myeloid malignant progression was not well characterized. In this study, we found that the patients of both myelodysplastic syndromes and chronic myeloid leukaemia with BMI1 overexpression had a higher risk in malignant myeloid progression. In vitro gene transfection studies showed that BMI1 inhibited cell myeloid and erythroid differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) and histone deacetylase inhibitor sodium butyrate respectively. BMI1 also resisted apoptosis induced by arsenic trioxide. Moreover, the transcript levels of Runx1 and Pten were down-regulated in Bmi1-transfected cells in company with histone deacetylation modification. By using chromatin immunoprecipitation (ChIP) collaborated with secondary generation sequencing and verified by ChIP-PCR, we found that BMI1 directly bound to the promoter region of Zmym3, which encodes a component of histone deacetylase-containing complexes. In addition, as one of the downstream target genes of this complex, c-fos was activated with increasing histone acetylation when ZMYM3 was suppressed in the Bmi1-transfected cells. These results suggested that BMI1 may reprogramme the histone acetylation profile in multiple genes through either indirect or direct binding effects which probably contributes to the malignant progression of myeloid progenitor cells.