As we have seen, the total mass of the histones associated with DNA in chromatin is about equal to that of the DNA. Interphase chromatin and metaphase chromosomes also contain small amounts of a complex set of other proteins. For instance, thousands of different transcription factors are associated with interphase chromatin. The structure and function of these critical nonhistone proteins, which regulate transcription, are examined in Chapter 9. Other low-abundance nonhistone proteins associated with chromatin regulate DNA replication during the eukaryotic cell cycle (see Chapter 19).

A few other nonhistone DNA-binding proteins are present in much larger amounts than the transcription or replication factors. Some of these proteins exhibit high mobility during electrophoretic separation and thus have been designated HMG (high-mobility group) proteins. When genes encoding the most abundant HMG proteins are deleted from yeast cells, normal transcription is disturbed in most genes examined. Some HMG proteins have been found to assist in the cooperative binding of several transcription factors to specific DNA sequences that are close to each other, stabilizing multiprotein complexes that regulate transcription of a neighboring gene, as discussed in Chapter 9.