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Gene specific overwriting of epigenetic signatures to modulate the expression of selected tumor-promoting genes in cancer

Authors
Publisher
BioMed Central
Volume
6
Identifiers
DOI: 10.1186/1756-8935-6-s1-p15
Keywords
  • Poster Presentation

Abstract

Gene specific overwriting of epigenetic signatures to modulate the expression of selected tumor-promoting genes in cancer POSTER PRESENTATION Open Access Gene specific overwriting of epigenetic signatures to modulate the expression of selected tumor-promoting genes in cancer Fahimeh Falahi1*, Christian Huisman1, Elisa Garcia Diaz1, Hinke G Kazemier1, Geke AP Hospers2, Marianne G Rots1 From Epigenetics and Chromatin: Interactions and processes Boston, MA, USA. 11-13 March 2013 Background Epidermal Growth Factor Receptor-2 (HER-2) and Estrogen receptor-alpha (ER-a) have been found to be dysregulated in several types of cancer. Their dysregula- tion is associated with aberrant epigenetic modifications. Additionally, expression of ER-a and HER-2 is inversely correlated; their crosstalk has been shown to be involved in endocrine therapy resistance mechanisms [1]. Thera- pies targeting either receptor result in cell proliferation inhibition for some cancer types; the anti-cancer effect might be further optimized to be more efficient and applicable for more cancer types by co-targeting the genes at the DNA level. As epigenetic modifications pro- vide a way to modify expression of genes in a sustained manner we aim to downregulate HER-2 and ER-a by inducing epigenetic silencing marks specifically onto their promoters (Epigenetic Editing [2]). We also aim to discover the possible crosstalk of ER-a with HER-2 and other important genes in cancer. Methods and materials Towards downregulation of HER-2 and ER-a, expression and epigenetic modification status of promoter of these genes were assessed in a panel of cancer cell lines (bisulfite sequencing and ChIP). Designed zinc finger proteins (ZFPs) targeting genes promoters were fused to a tran- scription repressor domain [SKD, histone methyltrans- ferases (G9a, SUV39H1), or a DNA methyltransferase domain (C141S [3])] and expressed in cancer cells through viral transduction. Results HER2-ZFP fused to G9a or SUV39H1 induced the intended sile

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