Epigenetic reprogramming of cancer cells via targeted DNA methylation.

Abstract	An obstacle in the treatment of human diseases such as cancer is the inability to selectively and effectively target historically undruggable targets such as transcription factors. Here, we employ a novel technology using artificial transcription factors (ATFs) to epigenetically target gene expression in cancer cells. We show that site-specific DNA methylation and long-term stable repression of the tumor suppressor Maspin and the oncogene SOX2 can be achieved in breast cancer cells via zinc-finger ATFs targeting DNA methyltransferase 3a (DNMT3a) to the promoters of these genes. Using this approach, we show Maspin and SOX2 downregulation is more significant as compared with transient knockdown, which is also accompanied by stable phenotypic reprogramming of the cancer cell. These findings indicate that multimodular Zinc Finger Proteins linked to epigenetic editing domains can be used as novel cell resources to selectively and heritably alter gene expression patterns to stably reprogram cell fate.
Authors	Ashley G Rivenbark, Sabine Stolzenburg, Adriana S Beltran, Xinni Yuan, Marianne G Rots, Brian D Strahl, Pilar Blancafort
Journal	Epigenetics (Epigenetics) Vol. 7 Issue 4 Pg. 350-60 (Apr 2012) ISSN: 1559-2308 [Electronic] United States
PMID	22419067 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	DNMT3A protein, human RNA, Small Interfering SERPIN-B5 SOX2 protein, human SOXB1 Transcription Factors Serpins DNA (Cytosine-5-)-Methyltransferases DNA Methyltransferase 3A
Topics	Base Sequence Breast Neoplasms (genetics, metabolism) Cell Line, Tumor Cell Proliferation Cell Survival DNA (Cytosine-5-)-Methyltransferases (genetics, metabolism) DNA Methylation DNA Methyltransferase 3A Epigenesis, Genetic Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Genes, Neoplasm Genetic Vectors (genetics, metabolism) Humans Lentivirus (genetics, metabolism) Promoter Regions, Genetic RNA, Small Interfering (genetics, metabolism) SOXB1 Transcription Factors (genetics, metabolism) Serpins (genetics, metabolism) Transfection Zinc Fingers

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