Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.

• GO:0007049 : cell cycle
• GO:0008283 : cell proliferation
• GO:0006281 : DNA repair
• GO:0010390 : histone monoubiquitination
• GO:0010216 : maintenance of DNA methylation
• GO:0000122 : negative regulation of transcription from RNA polymerase II promoter
• GO:0032270 : positive regulation of cellular protein metabolic process
• GO:2000373 : positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity
• GO:0045944 : positive regulation of transcription from RNA polymerase II promoter
• GO:0051865 : protein autoubiquitination
• GO:0042787 : protein ubiquitination involved in ubiquitin-dependent protein catabolic process
• GO:0006351 : transcription, DNA-dependent

Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/

Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/