Abstract
Abstract Heparanase is the only known enzyme that cleaves heparan sulfate (HS) and hence participates in the degradation and remodeling of the extracellular matrix (ECM). Pathological expression of heparanase at abnormal levels can contribute to the development of various diseases. In our research, directed by clustered regularly interspaced short palindromic repeats (CRISPR) system, the promoter region of heparanase was successfully and specifically targeted with screened and combined single guide RNAs (sgRNAs). Linking dCas9 with different histone modification enzymes (eg. P300, hHDAC3, LSD1), the expression of heparanase was successfully up- or down-regulated through acetylation, deacetylation and demethylation. This approach allows us to tune heparanase expression in various cell lines on demand, enabling the study of heparanase activity in real time. Citation Format: Guihua Zeng, Fu-Sen Liang, Lina Cui. Epigenetic control of heparanase expression through CRISPR/dCas9 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5234.
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