Chromosomes, chromatin, and the regulation of transcription

In eukaryotes, DNA is folded in a complex manner involving a number of successive stages or levels. Specifics of this folding are highly dynamic varying among cell types and organisms and within a single cell~for example, based on the stageof the cell cycle or local transcriptional activity. Transmission electron microscopy permits distinction between heterochromatin and euchromatin. Heterochromatin is relatively inactive transcriptionally, whereas euchromatin is relatively active. The first level of DNA folding into nucleosome-containing 10 nm filaments is the best understood. As a result, the relationship between nucleosomal organization of chromatin and transcriptional regulation has been at least partially elucidated. Similarly, folding of nucleosomecontaining filaments into 30 nm fibers is relatively well-understood. Since packing of chromatin into 30 nm fibers leads to general transcriptional inactivation, the role in transcriptional regulation of this level of higher-order chromatin structure seems clear. Much less clear is the role in transcriptional regulation of chromatin structure above the level of the 30 nanometer fiber. It is apparent that greater elucidation of this question will require detailed molecular characterization of nuclear architecture. To date, such details have not been forthcoming. However, recent technical advances and the availability of a number of specific probes should lead to novel insights in the immediate future.