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bioRxiv · 10.1101/093310

VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation

Artemov, A. V.·Zhigalova, N.·Zhenilo, S.·Mazur, A. M.·Prokhortchouk, E. B.
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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.

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Artemov, A. V., Zhigalova, N., Zhenilo, S., Mazur, A. M., Prokhortchouk, E. B.. 2016-12-12. VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation. https://doi.org/10.1101/093310

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