Structural basis for regulation of chromatin structure by DNA methylation

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The purpose of this study was to clarify the regulation of chromatin structures mediated by genome DNA methylation, and to investigate post-translational modifications of nuclear proteins by ubiquitin-like modifier proteins. We proceeded structural and functional analyses of the methylated DNA binding domain (MBD) of MBD1, the ubiquitin-like domain of human HR23B, and the ubiquitin-associated (UBA) domain of Saccharomyces cerevisae Rad23 and Lys 48- or Lys 63-linked di- or tetra-ubiquitin.We analyzed the dynamic property of the complex between MBD1 MBD and a methylated DNA by using NMR, SPR and isothermal calorimetry. We have determined solution structure of ubiquitin-like domain of human HR23B in complex with a ubiquitin interacting motif of proteasomal S5a subunit by NMR. We also determined solution structure of the complex between the UBA domain of yeast DSK2 and ubiquitin. In addition, we showed that show the difference in structural properties of Lys 48- or Lys 63-linked ubiquitin chains by isotope-aided NMR and small angle X-ray scattering.