title: RING finger protein 4 (RNF4) derepresses gene expression from DNA methylation.
abstract: 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.
authors.affiliation: From the Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115 yu.wang@childrens.harvard.edu.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D019175:DNA Methylation; D044127:Epigenesis, Genetic; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D055550:Protein Stability; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009687:Nuclear Proteins; C114070:RNF4 protein, human; D014157:Transcription Factors; D049452:Green Fluorescent Proteins
keywords: DNA Methylation; Methyl CpG-binding Protein 2 (MeCP2); Protein Turnover; RING Finger Protein 4 (RNF4); Transcription; Ubiquitylation (Ubiquitination)