Recent evidence from our laboratory indicates that the so-called "linker" histones (H1, H5, and their variants) can bind to certain DNA structures and sequences much more specifically than hitherto believed. In particular, these histones strongly bind to DNA crossover structures, typified by the four-way junction. These are the same structures favored by an abundant class of high mobility group proteins (HMG 1/2), and resemble the DNA structure at the entrance and exit from the nucleosome. Linker histones and HMG1 binding appear to be related to general mechanisms of genetic repression and expression. We propose a detailed investigation of this selective binding, including quantitation of binding by intact histones and their globular domains to the junction, and competition between histone variants and HMGI for such binding. The binding/competition experiments will then be extended to studies utilizing nucleosomes, as a more direct model of the in vivo structure. A second area of study will utilize PCR amplification methods in an attempt to discover DNA sequences or sequence types exhibiting strong linker histone binding. These will then be used in studies of the effects of such binding on DNA conformation.