?cl13008: Lge1_periphilin-like Superfamily
Eukaryotic transcriptional regulatory protein Lge1, periphilin, and similar proteins This family includes transcriptional regulatory protein Lge1 found in fungi as well as periphilin-1, a component of the Human Silencing Hub (HUSH) complex, a multiprotein complex that mediates epigenetic repression. In yeasts, Lge1 is involved in the ubiquitination of histones H2A and H2B. This ubiquitination step is a vital one in the regulation of the transcriptional activity of RNA polymerase II. In Saccharomyces cerevisiae, Rad6 and Bre1 are present in a complex that contains Lge1; this complex is required for H2B ubiquitination. Bre1 is the H2B ubiquitin ligase that interacts with acidic activators, such as Gal4, and recruits Rad6 and its binding partner Lge1 to target promoters. In Schizosaccharomyces pombe, the equivalent protein to Lge1 appears to be Shf1. In human, periphilin acts a transcriptional co-repressor and regulates cell cycle progression. In human, periphilin-1 is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It may act as transcriptional co-repressor involved in cell cycle progression. Chromosomal translocation of genes causing oncogenic fusion protein of Periphilin-1 and Fibroblast Growth Factor Receptor 2 (FGRF2) is associated with intrahepatic cholangiocarcinoma.
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