PHF8 Demethylates YY1 to Regulate ETC Gene and mROS to Promote Cancer Cell Growth

ABSTRACT: High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by electron transport chain (ETC). Targeting ETC represents a promising way of curing cancers. However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cell growth remain to be fully characterized. Here, we report that, while it is well-known to demethylate histones to activate transcription, demethylase PHF8 also functions as a co-repressor for a large set of ETC genes via demethylating the transcription factor YY1 at a highly conserved lysine (K) residue, K258. Consequently, PHF8–mediated YY1 demethylation is critical for regulating mROS production and cell growth in multiple types of cancer cells as well as tumor growth in cell line-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting PHF8/YY1 axis has great potential to treat cancers.

ORGANISM(S): Homo Sapiens

SUBMITTER: Wen Liu  

PROVIDER: PXD034400 | iProX | Tue Jun 07 00:00:00 BST 2022

REPOSITORIES: iProX