TY - JOUR T1 - VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation JF - bioRxiv DO - 10.1101/093310 SP - 093310 AU - Artem V. Artemov AU - Nadezhda Zhigalova AU - Svetlana Zhenilo AU - Alexander M. Mazur AU - Egor B. Prokhortchouk Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/12/12/093310.abstract N2 - VHL inactivation is a key oncogenic event for renal carcinomas. In normoxia, VHL suppresses HIF1a-mediated response to hypoxia. It has previously been shown that hypoxic conditions inhibit TET-dependent hydroxymethylation of cytosines and cause DNA hypermethylation at gene promoters. In this work, we performed VHL inactivation by CRISPR/Cas9 and studied its effects on gene expression and DNA methylation. We showed that even without hypoxia, VHL inactivation leads to hypermethylation of the genome which mainly occurred in AP-1 and TRIM28 binding sites. We also observed promoter hypermethylation of several transcription regulators associated with decreased gene expression. ER -