22 ACTIVATING TRANSCRIPTION (Full Edition)
1 Introduction
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- Eukaryotic gene expression is usually
controlled at the level of initiation of transcription.
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The phenotypic differences that distinguish the various kinds of cells in a higher
eukaryote are largely due to differences in the expression of genes that code for
proteins, that is, those transcribed by RNA polymerase II. In principle, the expression
of these genes might be regulated at any one of several stages. We can distinguish
(at least) five potential control points, forming the series:
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Activation of gene structure
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↓
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Initiation of transcription
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↓
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Processing the transcript
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Transport to cytoplasm
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↓
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Translation of mRNA
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Figure 22.1
Gene expression is controlled principally at the initiation of transcription, and
it is rare for the subsequent stages of gene expression to be used to determine
whether a gene is expressed, although control of processing may be used to determine
which form of a gene is represented in mRNA.
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As we see in Figure 22.1, gene expression in eukaryotes is largely controlled at
the initiation of transcription. For most genes, this is the major control point
in their expression. It involves changes in the structure of chromatin at the promoter
(see Promoter activation involves an ordered series of events), accompanied
by the binding of the basal transcription apparatus (including RNA polymerase II)
to the promoter. (Regulation at subsequent stages of transcription is rare in eukaryotic
cells. Premature termination occurs at some genes, and is counteracted by a kinase,
P-TEFb, but otherwise anti-termination does not seem to be employed.)
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The primary transcript is modified by capping at the 5′ end, and usually also
by polyadenylation at the 3′ end. Introns must be excised from the transcripts
of interrupted genes. The mature RNA must be exported from the nucleus to the cytoplasm.
Regulation of gene expression by selection of sequences at the level of nuclear
RNA might involve any or all of these stages, but the one for which we have most
evidence concerns changes in splicing; some genes are expressed by means of alternative
splicing patterns whose regulation controls the type of protein product (see Alternative
splicing involves differential use of splice junctions).
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Finally, the translation of an mRNA in the cytoplasm can be specifically controlled.
There is little evidence for the employment of this mechanism in adult somatic cells,
but it occurs in some embryonic situations. This can involve localization of the
mRNA to specific sites where it is expressed and/or the blocking of initiation of
translation by specific protein factors (see How are mRNAs and proteins transported
and localized?).
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Regulation of tissue-specific gene transcription lies at the heart of eukaryotic
differentiation; indeed, we see examples in Gradients, cascades, and signaling pathways
in which proteins that regulate embryonic development prove to be transcription
factors. A regulatory transcription factor serves to provide common control of a
large number of target genes, and we seek to answer two questions about this mode
of regulation: how does the transcription factor identify its group of target genes;
and how is the activity of the transcription factor itself regulated in response
to intrinsic or extrinsic signals?
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©Jones and Bartlett Publishers (2007)
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