In eukaryotic cells the histone methylase SUV39H1 and the methyl-lys binding protein HP1 interact to repress transcription at heterochromatic sites. Lys 9 of histone H3 is methylated by SUV39H1, creating a binding site for the chromo domain of HP1. The Lys methylase activity of SUV39H1 resides in the SET domain.SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. SUV39H1 cooperates with Rb to repress the cyclin E promoter, and in fibrobroblasts that are disrupted for SUV39, the activity of the cyclin E and cyclin A2 genes are specifcally elevated. Chromatin IPs (ChIPs) show that Rb is necessary to direct methylation of histone H3, and is necessary for binding of HP1 to the cyclin E promoter. The SUV39H1-HP1 complex is thus not only involved in heterochromatic silencing but also has a role in repression of euchromatic genes by Rb and perhaps other co-repressor proteins.
