More than SAM: mechanisms of action of the Polycomb group protein polyhomeotic

The Polycomb Group (PcG) system controls developmental transitions and cell states across species. Two main PcG complexes, Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2), regulate transcription and form epigenetic memory through chromatin. Polyhomeotic (Ph) is an essential PRC1 subunit that has received relatively little attention, perhaps because it is not implicated in either depositing or recognizing histone post-translational modifications (PTMs). Instead, Ph regulates chromatin architecture through its hallmark polymerizing sterile alpha motif (SAM). Here we review the biochemistry and function of Ph and mammalian polyhomeotic-like proteins (PHCs). We describe the role of SAM polymerization and evidence for essential polymerization-independent SAM functions. The evolutionary origins of Ph and possible co-evolution of disordered and ordered regions to maintain but modify Ph function are considered. Finally, we draw parallels between SAM function in animals and a recently discovered polymerization activity in a plant PcG protein that may reflect convergent evolution.