ATP-dependent chromatin structural modulation by multiprotein complex including HMGB1

High mobility group box protein 1, HMGB1, is a major nonhistone chromatin component in higher eukaryotic cells. HMGB1 is thought to be involved in the processes of global nuclear events such as transcription, recombination and repair, but the mechanism of these processes is unclear. Here, we show a concrete example of chromatin structural modulation by HMGB1 in HeLa S3 cells. A co-immunopurification experiment with Flag-tagged HMGB1 revealed that a portion of HMGB1 in HeLa S3 cells is included in a large-molecular-weight multiprotein complex. The multiprotein complex including HMGB1 showed ATP hydrolysis and ATP-dependent chromatin structural modulation activities that increased the susceptibility of chromatin to MNase digestion, while HMGB1 alone had no such activity. Thus, HMGB1 in the multiprotein complex is critical for expressing the chromatin structural modulation activity. These results suggest that HMGB1 is involved in chromatin structural modulation in global nuclear events through its interaction with a multiprotein complex in mammalian cells.