Structure of transcriptionally active chromatin

Transcriptionally active or potentially active genes can be distinguished by several criteria from inactive sequences. Active genes show both an increased general sensitivity to endonucleases like DNase I or micrococcal nuclease and the presence of nuclease hypersensitive sites. Frequently, the nuclease hypersensitive sites are present just upstream of the transcription initiation site covering sequences that are crucial for the promoter function. Viral or cellular transcription enhancer elements are also associated with DNase I hypersensitive sites. At least for the SV40 enhancer, it was shown by electronmicroscopic studies that the DNase I hypersensitive DNA segment is excluded from nucleosomes. It is highly plausible that the binding of regulatory proteins to enhancer or promoter sequences is responsible for the exclusion of these DNA segments from nucleosomes and for the formation of nuclease hypersensitive sites. We speculate that the binding of such proteins may switch on a change in the conformation and/or the protein composition of a chromatin segment or domain containing one to several genes. Biochemical analysis of fractionated nucleosome particles or of active and inactive chromatin fractions have revealed differences in the composition as well as in the degree of modification of histones in these two subfractions of the chromosome. However, until present it is impossible to define unambiguously what are the crucial structural elements that distinguish between particles present on active and inactive chromatin.