18.3: Additional Levels of Regulating Transcription
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Eukaryotes regulate transcription via promoter sequences close to the transcription unit (as in prokaryotes) and also use more distant enhancer sequences to provide more variation in the timing, level, and location of transcription, however, there are still additional levels of genetic control. This consists of two major mechanism: (1) large-scale changes in chromatin structure, and (2) modification of bases in the DNA sequence. These two are often inter-connected.
Chromatin Dynamics
Despite the simplified way in which we often represent DNA in figures such as those in this chapter, DNA is almost always associated with various chromatin proteins. For example, histones remain associated with the DNA even during transcription. Thus the rate of transcription is also controlled by the accessibility of DNA to RNApol and regulatory proteins. So, in regions were the chromatin is highly compacted, it is unlikely that any gene will be transcribed, even if all the necessary cis - and trans - factors are present in the nucleus. The extent of chromatin compaction in various regions is regulated through the action of chromatin remodeling proteins. These protein complexes include enzymes that add or remove chemical tags, such as methyl or acetyl groups, to various DNA bound proteins. These modifications alter the local chromatin density and thus the availability for transcription. Acetylated histones, for example, tend to be associated with actively transcribed genes, whereas deacetylated histone are associated with genes that are silenced (Figure \(\PageIndex{15}\)).
Likewise, methylation of DNA itself is also associated with transcription regulation. Cytosine bases, particularly when followed by a guanine ( CpG sites ) are important targets for DNA methylation (Figure \(\PageIndex{16}\)). Methylated cytosine within clusters of CpG sites is often associated with transcriptionally inactive DNA.
The modification of DNA and its associated proteins is enzymatically reversible (acetylation/deacetylation; methylation/demethylation) and thus a cyclical activity. Regulation of this provides another layer through which eukaryotic cells control the transcription of specific genes.