Human SFMBT is a transcriptional repressor protein that selectively binds the N-terminal tail of histone H3

Human SFMBT (hSFMBT) is postulated to be a Polycomb (PcG) protein. Similar to other PcG proteins, we found that hSFMBT displays robust transcriptional repressor activity. In addition, hSFMBT localized to the nucleus where it strongly associates with chromatin by directly and selectively binding the N-terminal tail of histone H3. Importantly, we discovered that the four tandem MBT repeats of hSFMBT were sufficient for nuclear matrix-association, N-terminal tail H3 binding, and required for transcriptional repression. These findings indicate that the tandem MBT repeats form a functional structure required for biological activity of hSFMBT and predict similar properties for other MBT domain-containing proteins.