Packaging of DNA as Nucleosomes in Eukaryotes

In any living system, the length of the DNA always greatly exceeds the dimensions of the compartment (e.g. nucleus), which contains it. The DNA (or RNA, as in some viruses) must, therefore, be compressed very tightly to fit into the space available. The density of DNA is about 10 mg/ml in bacteria, about 100 mg/ml in eukaryotic nucleus, and more than 500 mg/ml in T4 head. The overall compression of the DNA has also been described as packaging ratio (the length of DNA divided by the length of the unit that contains it). This packaging ratio in eukaryotes reaches 1000-2000 in interphase nuclei and upto 10,000 in metaphase nuclei. The patterns of this packaging and changes in these patterns during replication and transcription (gene expression) have been the subject of detailed study during the last more than three decades. These patterns of packaging are facilitated by associated proteins, which in eukaryotes, could be histones or nonhistones (RNA polymerase is also a nonhistone). More stable proteins in chromosomes are histones and are classified into five types called HI, H2A, H2B, H3 and H4. Another histone protein H5 (a variant of HI) has also been often described, although it may not be involved in packaging. It was thus known that chromatin consists of DNA, five different but stable proteins and a variety of nonhistone proteins.

It will be seen that the progress in the study of chromatin structure in early years, did not make much headway due to limitation of techniques. Whole mounts of chromosomes, whether within the cell or isolated, when examined under light or electron microscope, gave information about gross morphology including single stranded or multistranded nature or about the thickness of the ultimate single strands or fibres. When ultrathin sections of chromosomes were examined under electron microscope, it gave such an incomplete picture of chromatin structure that no satisfactory models could be prepared. Hundreds of speculatory models based on inadequate available data were presented and rejected before they could become known to students of cytology or genetics. However, in 1970's due to the use of improved techniques, nucleosome model for chromatin structure became available, which has been confirmed over and again during the last two decades. Some of the details regarding the techniques used for discovery of the nucleosome subunit, the structural details of this subunit and the higher levels of organization of these nucleosome subunits will be briefly discussed in this section.