@article {Artemov093310, author = {Artem V. Artemov and Nadezhda Zhigalova and Svetlana Zhenilo and Alexander M. Mazur and Egor B. Prokhortchouk}, title = {VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation}, elocation-id = {093310}, year = {2016}, doi = {10.1101/093310}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2016/12/12/093310}, eprint = {https://www.biorxiv.org/content/early/2016/12/12/093310.full.pdf}, journal = {bioRxiv} }