Open AccessBMI1 reprogrammes histone acetylation and enhances c‐fos pathway via directly binding to Zmym3 in malignant myeloid progression
Author(s) -
Shen Hongjie,
Chen Zixing,
Ding Xin,
Qi Xiaofei,
Cen Jiang,
Wang Yuanyuan,
Yao Li,
Chen Yan
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12246
Subject(s) - acetylation , bmi1 , histone , cancer research , myeloid , chemistry , biology , microbiology and biotechnology , biochemistry , stem cell , gene
The polycomb group BMI 1 is proved to be crucial in malignant myeloid progression. However, the underlying mechanism of the action of BMI 1 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 BMI 1 overexpression had a higher risk in malignant myeloid progression. In vitro gene transfection studies showed that BMI 1 inhibited cell myeloid and erythroid differentiation induced by 12‐O‐tetradecanoyl phorbol‐13‐acetate ( TPA ) and histone deacetylase inhibitor sodium butyrate respectively. BMI 1 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 (Ch IP ) collaborated with secondary generation sequencing and verified by Ch IP ‐ PCR , we found that BMI 1 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 ZMYM 3 was suppressed in the Bmi1‐ transfected cells. These results suggested that BMI 1 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.