MUTUAL STABILIZATION OF BACTERIOPHAGE-MU REPRESSOR AND HISTONE-LIKE PROTEINS IN A NUCLEOPROTEIN STRUCTURE

Integration host factor (IHF) binds in a sequence-specific manner to t he bacteriophage Mu early operator. It participates with bound Mu repr essor, c, in building stable, large molecular mass nucleoprotein compl exes in vitro and enhances repression of early transcription in vivo. We demonstrate that, when the specific IHF binding site with the opera tor is mutated, the appearance of large molecular mass complexes still depends on IHF and c, but the efficiency of their formation is reduce d. Moreover, the IHF-like HU protein, which binds DNA in a non-sequenc e-specific way can substitute for IHF and participate in complex forma tion. Since the complexes require both c and a host factor (IHF or HU) , the results imply that these proteins stabilise each other within th e nucleoprotein structures. These results suggest that IHF and HU are directed to the repressor-operator complexes, even in the absence of d etectable sequence-specific binding. This could be a consequence of th eir preferential recognition of DNA containing a distortion such as th at introduced by repressor binding to the operator. The histone-like p roteins could then stabilise the nucleoprotein complexes simply by the ir capacity to maintain a bend in DNA rather than by specific protein- protein interactions with c. This model is supported by the observatio n that the unrelated eukaryotic HMG-1 protein, which exhibits a simila r marked preference for structurally deformed DNA, is also able to par ticipate in the formation of higher-order complexes with c and the ope rator DNA.