P54. RYBP function in ES cells

Abstract

Polycomb group (PcG) proteins are necessary for the maintenance of transcriptional repression of a number of important developmental genes, including the homeotic genes. RYBP (Ring1 and YY1 Binding Protein) is a zinc finger protein, which interacts with the members of the mammalian polycomb complexes. RYBP is also a subunit of complexes containing transcription factors such as E2F6 and the embryonic stem (ES) pluripotency regulator Oct4. In addition, RYBP has been described as a positive regulator of apoptosis and in the apoptotic context, RYBP is known as DEDAF (death effector domain associated factor). RYBP is gene essential during embryonic development (its constitutive inactivation leads to an early embryonic lethal situation). We have generated a conditional inactivating ES cell line to study RYBP function in ES cells. Transcriptome analysis of RYBP-deficient cells identified a set of derepressed loci statistically correlated with a subset of upregulated genes in Dnmt1-deficient ES cells.TCHiP-chip analysis showed RYBP binding to a larger set of loci than those derepressed in RYBP-deficient ES cells, suggesting the involvement of redundant repressive mechanisms. RYBP silenced genes often show RYBP enrichment on nearby short CpG islands rather than on promoter regions. RYBP bound loci include many transposon-related repetitive sequence elements (IAP, MusD and MuERV) of which only those with a low CpG density are derepressed in the absence of RYBP. We are investigating a possible role of RYBP on the establishment of gene repression patterns stabilized by DNA methylation during ES cell differentiation.