Chromatin Structure and Gene Regulation

One type of gene control in eukaryotic cells is accomplished through the modification of gene structure. In the nucleus, histone proteins associate to form octamers, around which helical DNA tightly coils to create chromatin (see Figure 11.5). In a general sense, this chromatin structure represses gene expression. For a gene to be transcribed, transcription factors, activators, and RNA polymerase must bind to the DNA. How can these events take place with DNA wrapped tightly around histone proteins? The answer is that before transcription, chromatin structure changes, and the DNA becomes more accessible to the transcriptional machinery.

DNase I hypersensitivity Several types of changes are observed in chromatin structure when genes become tran-scriptionally active. One type is an increase in the sensitivity of chromatin to degradation by DNase I, an enzyme that digests DNA. When tightly bound by histone proteins, DNA is resistant to DNase I digestion because the enzyme cannot gain access to the DNA. When DNA is less tightly bound by histones, it becomes sensitive to DNase I degradation. Thus, the ability of DNase I to digest DNA provides an indication of the DNA-histone association.

As genes become transcriptionally active, regions around the genes become highly sensitive to the action of DNase I (see Chapter 11). These regions, called DNase I hypersensitive sites, frequently develop about 1000 nu-cleotides upstream of the start site of transcription, suggesting that the chromatin in these regions adopts a more open configuration during transcription. This relaxation of the chromatin structure may allow regulatory proteins access to binding sites on the DNA. Indeed, many DNase I hypersensitive sites correspond to known binding sites for regulatory proteins.

Histone protein

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