PT  - JOURNAL ARTICLE
AU  - Artem V. Artemov
AU  - Nadezhda Zhigalova
AU  - Svetlana Zhenilo
AU  - Alexander M. Mazur
AU  - Egor B. Prokhortchouk
TI  - VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
AID  - 10.1101/093310
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 093310
4099  - http://biorxiv.org/content/early/2016/12/12/093310.short
4100  - http://biorxiv.org/content/early/2016/12/12/093310.full
AB  - 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.