Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome

model building and other predictive structural analysis. The proposal made 25 years ago that chromatin struc-The histones came to be regarded as an amorphous ture is based on a repeating unit of eight histone mole-coating or passive polymeric counterion of the DNA. cules and about 200 DNA base pairs (Kornberg, 1974) Ironically, the very breakthrough of acid extraction, laid the basis for subsequent chromatin research. During which clarified the molecular composition of the his-the past few years, the X-ray structure of the repeating tones, at the same time denatured them and impeded unit, termed the nucleosome, has been solved (Arents further studies. Once denatured, elucidation of their et al., 1991; Luger et al., 1997), and its biologic signifi-structure and biochemistry was doomed. With the ad-cance has emerged. The nucleosome is a focal point of vent of powerful protease inhibitors, histones could be transcription control, uniting previously disparate obser-extracted by milder methods (Van Der Westhuyzen and vations on gene activation and repression at the level Von Holt, 1971), leading to the discovery of an (H3) 2 (H4) 2 of individual promoters, transcription units, and whole Bell and histone oligomers could be recombined with DNA to Felsenfeld, 1999). Connections with DNA replication and generate the characteristic X-ray diffraction pattern the cell cycle, with recombination and other DNA trans-of chromatin; both types of oligomer were required, actions, and with viral infection and cancer have become whereas the H1 histone was not (Kornberg and Thomas, apparent as well. This convergence of structural and 1974). functional studies gives occasion to celebrate the silver anniversary of the nucleosome. The Nucleosome The organizing principle of the nucleosome, a histone The Histones octamer, and its mode of interaction with DNA were The initial impact of the nucleosome idea was to dispel deduced from the properties of the tetramer, as follows an aura of mystery surrounding the histones, whose (Kornberg, 1974): existence was recognized in the last century (Kossel, (1) The stoichiometry of the tetramer indicated that 1884). As universal components of eukaryote chromo-apparent deviations from equimolar amounts of H2A, somes, histones were found at a mass level roughly H2B, H3, and H4 in chromatin could be disregarded, equal to that of the DNA; in fact, the histones were long and it further implied a repeating unit that contained viewed as the genetic material itself, and later as diverse two each of the histones. The requirement for all four …