Histone Lysine Methylation Dynamics Control EGFR DNA Copy-Number Amplification.

ABSTRACT: Acquired chromosomal DNA copy gains are a feature of many tumors; however, the mechanisms that underpin oncogene amplification are poorly understood. Recent studies have begun to uncover the importance of epigenetic states and histone lysine methyltransferases (KMT) and demethylases (KDM) in regulating transient site-specific DNA copy-number gains (TSSG). In this study, we reveal a critical interplay between a myriad of lysine methyltransferases and demethylases in modulating H3K4/9/27 methylation balance to control extrachromosomal amplification of the EGFR oncogene. This study further establishes that cellular signals (hypoxia and EGF) are able to directly promote EGFR amplification through modulation of the enzymes controlling EGFR copy gains. Moreover, we demonstra

SUBMITTER: Clarke TL 

PROVIDER: S-EPMC7271978 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature