Three-dimensional arrangements of chromatin and chromosomes: Old concepts and new techniques

The studies of early cytologists, well before the turn of this century, indicated that the positions of mitotic chromosomes in a particular metaphase cell correlated with their respective positions in preceding cell divisions. Observations of this type led to the concept that metaphase chromosomes were not simply aggregations of dispersed chromatin. Furthermore, when it became clear that chromosomes were the carriers of the genetic material many ideas developed relating the arrangement of chromosomes to gene expression in nuclei. A major problem in analysing interphase nuclei was the difficulty in visualizing chromosomes at this stage in the cell cycle. Recent advances in combining the techniques of molecular biology with modifications to the optical microscope and computer image enhancement, analysis and interpretation have revolutionized the capability of studying the very old problem of whether order exists within the eukaryote nucleus.