Human SFMBT binds the N‐terminal tail of histone H3 to induce transcriptional repression of specific target genes

Abstract

We recently discovered that human SFMBT (hSFMBT), which contains a tandem array of four conserved MBT domains, is a potent repressor of transcription. In addition, we found that hSFMBT partitions to the nucleus where it strongly associates with the insoluble chromatin of the nuclear matrix and selectively binds the N‐terminal tail of histone H3. Importantly, we discovered that all four 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. We hypothesize that hSFMBT is targeted to specific genomic regions to maintain a transcriptionally repressive state. Consistent with this, we have recently identified several candidate genes regulated by hSFMBT and are currently verifying these findings. In addition, we recently found that hSFMBT exists in an ~700 kDa complex using conventional chromatography techniques. Ongoing studies aim to identify these proteins and determine their functional significance.