The nature of protein association with chromatin.

The reality of the nonrandom distribution of histones along the chromatin strand was investigated in several ways. It does not appear to derive from histone exchange during shearing and is evident in chromatin fixed with formaldehyde prior to shearing. Endogenous or Escherichia coli polymerase are preferentially associated with regions of chromatin with a low protein/DNAratio. Although RNA polymerase and histones are fixed to chromatin after formaldehyde treatment with high efficiency, only a minor fraction of non-histone protein is fixed under similar conditions. Even after washing in high salt to minimize adventitious association, most remaining non-histone protein fails to be fixed. The utility of this approach for defining chromosomal proteins is discussed.