RT Journal Article
SR Electronic
T1 VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 093310
DO 10.1101/093310
A1 Artem V. Artemov
A1 Nadezhda Zhigalova
A1 Svetlana Zhenilo
A1 Alexander M. Mazur
A1 Egor B. Prokhortchouk
YR 2016
UL http://biorxiv.org/content/early/2016/12/12/093310.abstract
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.