Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-03590-5
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Funding
- National Science Foundation of China [81502250, 81600448, 81472783, 81230038, 81372801, 81772787, 81572570, 81272426]
- '973' Program of China [2015CB553903]
- National Science-technology Support Projects [2015BAI13B05]
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Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBP beta, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBP beta, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBP beta can maintain an open chromatin state by H3K79 methylation of multiple drug- resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBP beta may provide more precise therapeutic options in ovarian cancer.
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