Folding up genes and chromosomes

The basic chromatin fiber is composed of a tandem array of nucleosomes, adjacent nucleosomes being separated by a variable amount of DNA. In vivo, this fiber is folded to form a higher-order fiber with a diameter of 200 to 300 A. The distribution of nucleosomes within the higher-order fiber has been analyzed in negatively stained preparations of chromatin fibers released from metaphase cells or interphase nuclei by mechanical disruption. The fiber appears to be composed to discrete packing domains in each of which there is a high density of closely apposed nucleosomes; within these regions several discrete packing patterns are observed. Adjacent domains are connected by regions of the fiber which are thinner and contain a lower density of nucleosomes. From these observations we suggest that the 200 to 300 A fiber is mosaic and that domains differ from each other in composition so as to confer sequence specificity upon the structure. In addition, compositional differences may have relevance to the functional state of the underlying genes; thus, higher order structure of a region is related to its functional state. Above this level of organization, studies on the early stages of chromatin folding in meiotic prophase suggest that 200 to 300 A fibers are organized as loops which emanate from the longitudinal axis of the chromosome, in a manner consistent with a model for mitotic chromosome folding by means of radial loop formation. Active ribosomal RNA genes are identifiable in these preparations and appear to be organized in a similar fashion; each active gene appears to comprise a loop of chromatin.