Epigenetic and non-epigenetic functions of the RYBP protein in development and disease.

Over the last decades significant advances have been made in our understanding of the molecular mechanisms controlling organismal development. Among these mechanisms the knowledge gained on the roles played by epigenetic regulation of gene expression is extensive. Epigenetic control of transcription requires the function of protein complexes whose specific biochemical activities, such as histone mono-ubiquitylation, affect chromatin compaction and, consequently activation or repression of gene expression. Complexes composed of Polycomb Group (PcG) proteins promote transcriptional silencing while those containing trithorax group (trxG) proteins promote transcriptional activation. However, other epigenetic protein factors, such as RYBP, have the ability to interact with both PcG and trxG and thus putatively participate in the reversibility of chromatin compaction, essential to respond to developmental cues and stress signals. This review discusses the developmental and mechanistic functions of RYBP, a ubiquitin binding protein, in epigenetic control mediated by the PcG/trxG proteins to control transcription. Recent experimental evidence indicates that proteins regulating chromatin compaction also participate in other molecular mechanisms controlling development, such as cell death. This review also discusses the role of RYBP in apoptosis through non-epigenetic mechanisms as well as recent investigations linking the role of RYBP to apoptosis and cancer.