HMG-D IS AN ARCHITECTURE-SPECIFIC PROTEIN THAT PREFERENTIALLY BINDS TO DNA CONTAINING THE DINUCLEOTIDE TG

The high mobility group (HMG) protein HMG-D from Drosophila melanogast er is a highly abundant chromosomal protein that is closely related to the vertebrate HMG domain proteins HMG1 and HMG2. In general, chromos omal HMG domain proteins lack sequence specificity. However, using bot h NMR spectroscopy and standard biochemical techniques we show that bi nding of HMG-D to a single DNA site is sequence selective. The preferr ed duplex DNA binding site comprises at least 5 bp and contains the de formable dinucleotide TG embedded in A/T-rich sequences. The TG motif constitutes a common core element in the binding sites of the well-cha racterized sequence-specific HMG domain proteins. We show that a conse rved aromatic residue in helix 1 of the HMG domain may be involved in recognition of this core sequence. In common with other HMG domain pro teins HMG-D binds preferentially to DNA sites that are stably bent and underwound, therefore HMG-D can be considered an architecture-specifi c protein. Finally, we show that HMG-D bends DNA and may confer a supe rhelical DNA conformation at a natural DNA binding site in the Drosoph ila fushi tarazu scaffold-associated region.