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Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements


Polycomb Group (PcG) proteins are epigenetic repressors essential for development and cell differentiation. PcG proteins form five complexes targeted to specific genes by Polycomb Response Elements (PREs). How PcG complexes are recruited to PREs is poorly understood. Here we investigate the recruitment of PhoRC, a seemingly simple case of a complex that contains a sequence-specific DNA binding subunit: PHO (or the related protein PHOL). Unexpectedly, we find that the sequence specific binding of PHO is not a primary determinant for recruitment of PhoRC to PRE, which depends on the non-DNA binding subunit SFMBT and cross-talk with another PcG complex, PRC1. The binding of PhoRC is helped by PRC1 and, in turn, may stabilize the binding of PRC1. We propose that the recruitment based on combinatorial interactions enables the conditional binding of PcG proteins, which is important for switching the state of the target genes from repressed to active. The critical role of the cross-talk between PhoRC and PRC1 is further supported by the finding that in mammals, where the protein domains linking the two complexes are missing, the PHO ortholog YY1 has no implication in PcG repression, despite 100% conservation between DNA binding domains of YY1 and PHO.


Vyšlo v časopise: Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004495
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004495

Souhrn

Polycomb Group (PcG) proteins are epigenetic repressors essential for development and cell differentiation. PcG proteins form five complexes targeted to specific genes by Polycomb Response Elements (PREs). How PcG complexes are recruited to PREs is poorly understood. Here we investigate the recruitment of PhoRC, a seemingly simple case of a complex that contains a sequence-specific DNA binding subunit: PHO (or the related protein PHOL). Unexpectedly, we find that the sequence specific binding of PHO is not a primary determinant for recruitment of PhoRC to PRE, which depends on the non-DNA binding subunit SFMBT and cross-talk with another PcG complex, PRC1. The binding of PhoRC is helped by PRC1 and, in turn, may stabilize the binding of PRC1. We propose that the recruitment based on combinatorial interactions enables the conditional binding of PcG proteins, which is important for switching the state of the target genes from repressed to active. The critical role of the cross-talk between PhoRC and PRC1 is further supported by the finding that in mammals, where the protein domains linking the two complexes are missing, the PHO ortholog YY1 has no implication in PcG repression, despite 100% conservation between DNA binding domains of YY1 and PHO.


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