Epigenomic Analysis in a Cell-Based Model Reveals the Roles of H3K9me3 in Breast Cancer Transformation

Abstract

Aim: Epigenetic marks are critical regulators of chromatin and gene activity. Their roles in normal physiology and disease states, including cancer development, still remain elusive. Herein, the epigenomic change of H3K9me3, as well as its potential impacts on gene activity and genome stability, was investigated in an in vitro breast cancer transformation model. Methods: The global H3K9me3 level was studied with western blotting. The distribution of H3K9me3 on chromatin and gene expression was studied with ChIP-Seq and RNA-Seq, respectively. Results: The global H3K9me3 level decreases during transformation and its distribution on chromatin is reprogrammed. By combining with TCGA data, we identified 67 candidate oncogenes, among which five genes are totally novel. Our analysis further links H3K9me3 with transposon activity, and suggests H3K9me3 reduction increases the cell’s sensitivity to DNA damage reagents. Conclusion: H3K9me3 reduction is possibly related with breast cancer transformation by regulating gene expression and chromatin stability during transformation.

Keywords::

• breast cancer transformation
• epigenomics
• genome stability
• H3K9me3
• transcription regulation

Supplementary data

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Financial & competing interests disclosure

This work was supported by grants from the Ministry of Science and Technology of China (2016YFA0502100), National Natural Science Foundation of China to M Wu (31470771 and 31521091) and L Li (31370866, 31540013 and 31670874). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the Ministry of Science and Technology of China (2016YFA0502100), National Natural Science Foundation of China to M Wu (31470771 and 31521091) and L Li (31370866, 31540013 and 31670874). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.