High-mobility group protein 2 may be involved in the locus control region regulation of the β-globin gene cluster

Expression regulation of the β-globin gene cluster is a result of synergistic interactions between cis-elements and trans-acting factors. Previous studies usually concentrated on the core sequence of each hypersensitive site in the locus control region of the β-globin gene cluster. But more and more evidence illustrates that the flanking regions are indispensable also. Using electrophoretic mobility shift assay and solid-phase DNase I footprinting methods, we identified a small nuclear protein from K562 cells that binds specifically to the first AT-rich region flanking the hypersensitive site 2 core sequence of the human β-globin gene locus control region. N-terminal sequencing of the enriched protein proved that it is a member of the high-mobility group protein 2 family. This indicates that the AT-rich region in human hypersensitive site 2 may take part in the regulation of the β-globin gene cluster by facilitating DNA bending, which is a prerequisite for the looping mechanism in this region.Key words: β-globin gene, locus control region, hypersensitive site 2, AT-rich region, high-mobility group protein 2.