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Although the nucleosomal core particle has been extensively studied as the basic building block of chromatin, the biological significance of a unit carrying exactly 146 bp of DNA remains unclear. Herein, we present data to show that the histone octamer can stably accommodate anywhere from about 100 to 170 bp of DNA. The unfolded structures containing less than 146 bp may well be of greater biological importance than the canonical core particle.

The linker histones (H1, H1 zero, H5, etc.) and a group of abundant non-histone chromosomal proteins (HMG1/2) bind to linker DNA in chromatin and exhibit both generalized and specific effects on gene transcription. The two classes of proteins share many features of DNA binding behaviour, although they are structurally unrelated. While the linker histones and HMG1/2 exhibit direct competition in binding to such structures as four-way junction DNA, whether they compete for binding to the nucleosome has not been investigated. The possibility for either opposite or synergistic effects on gene regulation must be considered at this point.

It has long been assumed that the architectural proteins of chromatin (the histones, for example) are unrelated to their functional proteins (transcription factors, polymerases, etc). New studies(1,2) drastically change this perspective. It appears that a portion of the general transcription initiation complex TFIID is made up of proteins that not only carry marked sequence and structural resemblances to the core histones of the nucleosome, but also form an octameric complex similar to the histone octamer. This can now be seen as part of a general pattern of continuity among structural and functional chromatin proteins.

Extensive studies of DNA secondary structure during the past decade have shown that DNA is a dynamic molecule, whose structure depends on the underlying nucleotide sequence and is influenced by the environment and the overall DNA topology. Three major non-B-DNA structures have been described (Z-DNA, triplex DNA and cruciform DNA) which are stabilized by unconstrained negative supercoiling and can be formed under physiological conditions. In this essay we summarize the DNA primary structure features that are pertinent to the formation of these conformers and present data concerning the occurrence of these sequences in the eukaryotic genome. The evidence in favor of the existence of these unusual DNA structures in vivo is discussed. The effect of alternative non-B-DNA structures on the way DNA is organized in chromatin is considered, and this is followed by evaluation of the data relating these structures to eukaryotic transcription. Some possible mechanisms by which the effect of non-B structures on transcription might be exerted are proposed.