| The role of the evolutionarily conserved SWIRM domain in the lysine specific demthylase LSD1 is not well understood, as the amine oxidase domain contains the active site. It was shown here that the SWIRM domain binds histone H3 and H3 N-terminal peptides with some, but not all, of the known modifications. However, the SWIRM and amine oxidase domains must be combined to repress transcription. The NMR structure of the isolated LSD1 SWIRM domain was determined and chemical shift perturbations gave a dissociation constant of 2.3x10-4M for binding an H3 peptide. A model of the SWIRM domain and H3 peptide showed the peptide bound in a groove on the SWIRM domain located at the interface with the amine oxidase domain. These data suggest that the SWIRM domain plays an initial role in binding H3 N-terminal tails prior to activating LSD1.;Other binding partners of LSD1 have been found recently, such as human androgen receptors. Our preliminary data show that the SWIRM domain may have a direct interaction with the DNA binding domain of human androgen receptors, while other evidence needs to be provided.;The methyltransferase SET8 plays a role in regulating the cell cycle by suppressing DNA replication through histone binding. SET8 can bind to the N-terminal tail of H4 through its histone binding domain (HBD) based on our NMR titration results. Such binding has been approved to block the hyperacetylation on H4NT, focusing on residues Lys5, Lys8 and Lys12. Compared with previous determined SET family structures, HBD should belong to N-flanking domain of SET8, perhaps helping to stabilize the structure of the SET module and target on specific substrates. HBD localizes in the nucleus, especially concentrating in the nucleolus. Combined with NMR results, the residues on the C-terminal of HBD contribute a lot to the association between HBD and H4NT. |
