Homeoprotein DNA-binding specificity

In marked contrast to their precise target recognition in vivo, in vitro, homeoproteins bind DNA quite promiscuously. In their upcoming paper, Dr. Abate-Shen and colleagues demonstrate that the PIAS1 SUMO E3 ubiquitin ligase protein underlies the in vivo DNA-binding specificity of the Msx1 homeoprotein.

The researchers show that the interaction between Msx1 and PIAS1 (but not its sumoylation) is required for Msx1 localization to the nuclear periphery of muscle precursor cells. There, Msx1 is posited to bind its targets genes, MyoD and Myf5, and regulate muscle cell differentiation.

Dr. Abate-Shen explains that “Our studies go a long way towards unraveling the mystery of how homeoproteins can find their target genes in vivo and, in addition, help pus to understand how the “address” of a gene in the nucleus contributes to its differential regulation.”