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Key concepts Regulation of Transcription in Eukaryotes
Because of the demands of development and of responding to environmental factors, the regulation of
transcription is much more complex in eukaryotes than in viruses or bacteria.
Promoter regions in eukaryotes are usually split into core and proximal elements; the core contains the
polymerase docking site, while the proximal promoter region has regulatory functions.
Distal DNA regulatory elements include enhancers, silencers, insulators, and locus control regions. Each
of these elements acts through its own mechanisms.
Eukaryotic transcription factors are molecular complexes that bind to DNA regulatory elements.
Typically, they contain both DNA-binding and activation domains that act to bind to specific DNA
sequences in specific genes and then activate transcription through recruitment of the basal
transcriptional machinery.
There are also protein factors that help polymerases to pass through nucleosomes. The mechanisms for
transcription of DNA within nucleosomes are still not well understood.
Transcription in eukaryotes is markedly influenced by post-translational modification or marking of
histones on nucleosomes. These marks include acetylation, methylation, phosphorylation,
ubiquitylation, and poly(ADP)ribosylation events. Specific enzymes exist for each of these modifications:
the enzymes are highly specific for individual amino acid residues on individual histone molecules. There
is also cross-talk between such modifications.
Specific readers of these markings exist that, upon recognizing the marks, initiate the modification of
gene expression. Certain modifications, like lysine acetylation, correlate strongly with gene activity.
Others are associated with gene silencing.
Histone replacement variants also play a role in gene regulation. For example, H2A.Z is often found in
nucleosomes that flank nucleosome-free regions, which occur around transcription start sites. H3.3 and
H2A.Bbd are often associated with active transcription.
Chromatin structure must sometimes be remodeled to permit transcription. This can be accomplished
by a battery of ATP-dependent chromatin remodelers. These may slide nucleosomes on DNA, modify
their structure, or partly dissociate the nucleosomal particle.
In addition to all the other mechanisms described above, it is now becoming clear that long noncoding
RNAs can carry out a remarkable number of regulatory functions.