RNF4 is an E3 ubiquitin ligase originally identified as a transcription co-activator. The mechanism by which RNF4 promotes transcription remains unclear. In this study, I found that RNF4 antagonizes transcriptional repression mediated by DNA methylation. RNF4 does not promote DNA demethylation, but mediates the ubiquitination of MeCP2, a methyl-CpG-binding domain (MBD) protein. Removal of MeCP2 from gene promoters activates transcription. This study thus not only uncovers how RNF4 functions as a transcription activator, but also reveals the mechanism by which MeCP2 protein stability is regulated.
Keywords: DNA Methylation; Methyl CpG-binding Protein 2 (MeCP2); Protein Turnover; RING Finger Protein 4 (RNF4); Transcription; Ubiquitylation (Ubiquitination).
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.