| The histone code regulates a number of processes including transcription, DNA replication, and DNA repair. L3MBTL3 is a putative histone code reader that possesses methyl-lysine binding MBT domains. This study commences with the cellular characterization of UNC1215, the first potent and selective chemical probe targeting a methyl-lysine reader domain, the MBT domains of L3MBTL3. Once established as a potent, selective, and cell-active chemical probe, UNC1215 was used to study the biological function of L3MBTL3. L3MBTL3 was shown to bind histone H3 and to associate with the repressive BHC complex in HEK293 cells and in the erythroid leukemia K562 cell line. Possibly via its association with this complex, L3MBTL3 impairs megakaryopoiesis in a manner dependent on its MBT domains. Additionally, L3MBTL3 may promote erythroid development. In summary, this study utilized cell and chemical biology approaches to obtain insights into the mechanistic function of L3MBTL3, and uncover a role in repressing megakaryopoiesis. |
