Chromodomains of PRC1: dPc and its mammalian homolog, CBX2


Polycomb group (PcG) proteins are conserved epigenetic transcriptional regulators that maintain the transcriptional repression of silenced genes. According to the polycomb-signaling model, H3K27me3 is deposited by PRC2 and is then recognized by the chromodomain-containing lysine methylation reader subunit of Polycomb Repressive Complex 1 (PRC1), which is Polycomb (Pc) in Drosophila melanogaster and  Chromobox homologs (CBXs) in mammals. Upon recognition and binding of dPc subunit to the H3K27me3 mark, other PRC1 subunits such as Ph, Psc and dRing are recruited, resulting in the nucleosome compaction and inhibition of remodeling complexes and transcription. HP1, another chromodomain containing protein, is involved in epigenetic repression of gene expression in D. melanogaster, which can recognize and bind H3K9me3 marks. Fischle et al. (2003) demonstrated that binding of Pc to mono- or dimethylated Lys 27 peptides was about five times weaker than binding to the trimethylated Lys 27 peptide, but still much stronger than binding to the trimethylated Lys 9 peptide. Furthermore, no significant interactions were observed between the Pc chromodomain and mono- or dimethylated Lys 9 peptides. On the other hand, HP1's binding affinity for dimethyl- and monomethyl-Lys 9  or lysine27 and also H3K27me3 is much lower compared to its binding to H3K9me3 (Fischle et al. 2003), indicating that the degree of methylation affects binding of both dPc and HP1 to their target sites and that the trimethylated lysine is the preferred level of methylation for both proteins in vitro.