A major emphasis will be placed on relating our studies of nucleosome heterogeneity to nucleosome function. For this purpose we plan the 3 following major aims: 1. To determine the distribution of specific DNA sequences among different electrophoretic forms of nucleosomes. One system we are studying is the mouse beta-globin gene in cell lines which are either producing or not producing hemoglobin. Recombinant DNA's will be used as hybridization probes in these experiments. 2. To determine whether specific proteins (minor histone Ml, HMG-17) are associated with nucleosomes along specific DNA sequences. Antibodies raised against purified chromosomal proteins will be used to isolate nucleosome possessing stoichiometric amounts of certain proteins. DNA sequences originating from these nucleosome subsets will be examined. 3. To determine whether specific chromosomal proteins (e.g. HMG-17) can reassociate with nucleosomes in a non-random manner with regard to expressed DNA sequences.