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12. Regulation of Genome Activity
Learning outcomes
When you have read Chapter 12, you should be able to:
1. Distinguish between differentiation and development, and outline how regulation of genome
expression underlies these two processes
2. Describe, with examples, the various ways in which extracellular signaling compounds can bring
about transient changes in genome activity, making clear distinction between those signaling
compounds that enter the cell and those that bind to a cell surface receptor
3. Describe, with examples, the various ways in which permanent and semipermanent changes in
genome activity can be brought about, making clear distinction between those processes that
involve rearrangement of the genome, those that involve changes in chromatin structure, and
those that involve feedback loops
4. Discuss how studies of sporulation in Bacillus subtilis, vulva development in Caenorhabditis
elegans, and embryogenesis in Drosophila melanogaster have contributed to our understanding of
genome regulation during development, and explain why lower organisms can act as models for
development in higher eukaryotes such as humans
Figure 12.1. Two ways in which
genome activity is regulated. The
genes on the left are subject to
transient regulation and are
switched on and off in response
to changes in the extracellular
environment. The genes on the
right
have
undergone
a
permanent or semipermanent
change in their expression
pattern, resulting in the same
three genes being expressed
continuously.
12.1. Transient Changes in Genome Activity
12.2. Permanent and Semipermanent Changes in Genome Activity
12.3. Regulation of Genome Activity During Development
12.1. Transient Changes in Genome Activity
12.2. Permanent and Semipermanent Changes in Genome Activity
Figure 12.2. Two ways in which an extracellular signaling compound can
influence events occurring within a cell.
Figure 12.3. Three ways in which an extracellular signaling compound could
influence genome activity
Figure 12.4. Copper-regulated gene expression in Saccharomyces cerevisiae. Yeast requires low amounts of copper
because a few of its enzymes (e.g. cytochrome c oxidase and tyrosinase) are copper-containing metalloproteins,
but too much copper is toxic for the cell. When copper levels are low, the Mac1p protein factor is activated by
copper binding and switches on expression of genes for copper uptake. When the copper levels are too high, a
second factor, Ace1p, is activated, switching on expression of a different set of genes, these coding for proteins
involved in copper detoxification.
Figure 12.5. Gene activation by a steroid hormone. Estradiol is one of the estrogen steroid
hormones. After entering the cell, estradiol attaches to its receptor protein and the complex enters
the nucleus where it binds to the 15-bp estrogen response element (abbreviation: N, any
nucleotide), which is located upstream of those genes activated by estradiol and other estrogens.
Other steroid hormone receptors recognize other response elements. For example, glucocorticoid
hormones target the sequence 5′-AGAACANNNTGTTCT-3′. Note that this sequence, and that of the
estrogen response element, is an inverted palindrome. The response element for vitamin D3,
which is a steroid derivative that activates transcription via a nuclear receptor (see the text), has
the sequence 5′-AGGTCANNNAGGTCA-3′, which is a direct repeat rather than an inverted
palindrome.
Figure 12.6. All steroid hormone receptor proteins have similar structures. Three
receptor proteins are compared. Each one is shown as an unfolded polypeptide with
the two conserved functional domains aligned. The DNA-binding domain is very similar
in all steroid receptors, displaying 50–90% amino acid sequence identity. The hormonebinding domain is less well conserved, with 20–60% sequence identity. The activation
domain (Section 9.3.2) lies between the N terminus and the DNA-binding domain, but
this region displays little sequence similarity in different receptors.
Figure 12.7. Catabolite repression. (A) A typical diauxic growth curve, as seen when
Escherichia coli is grown in a medium containing a mixture of glucose and lactose.
During the first few hours the bacteria divide exponentially, using the glucose as
the carbon and energy source. When the glucose is used up there is a brief lag
period while the lac genes are switched on before the bacteria return to
exponential growth, now using up the lactose. (B) Glucose overrides the lactose
repressor. If lactose is present then the repressor detaches from the operator and
the lactose operon should be transcribed, but it remains silent if glucose is also
present. Refer to Figure 9.24B for details of how the lactose repressor controls
expression of the lactose operon. (C) Glucose exerts its effect on the lactose
operon and other target genes by controlling the activity of adenylate cyclase and
hence regulating the amount of cAMP in the cell. The catabolite activator protein
(CAP) can attach to its DNA-binding site only in the presence of cAMP. If glucose is
present, the cAMP level is low, so CAP does not bind to the DNA and does not
activate the RNA polymerase. Once the glucose has been used up, the cAMP level
rises, allowing CAP to bind to the DNA and activate transcription of the lactose
operon and its other target genes.
Figure 12.8. The role of a cell surface receptor in signal transduction. Binding of the
extracellular signaling compound to the outer surface of the receptor protein causes a
conformational change that results in activation of an intracellular protein, for example
by phosphorylation. The events occurring ‘downstream' of this initial protein activation
are diverse, as described in the text. ‘P' indicates a phosphate group, PO32-.
Figure 12.9. Signal transduction involving
STATs. (A) If the receptor is a member of
the tyrosine kinase family then it can
activate the STAT directly. (B) If the
receptor is a tyrosine-kinase-associated
type then it acts via a Janus kinase (JAK),
which autophosphorylates when the
extracellular signal binds and then
activates the STAT. Note that activation
of the JAK usually involves dimerization,
the extracellular signal inducing two
subunits to associate, resulting in the
version of the JAK with phosphorylation
activity. Dimerization is also central to
activation of a STAT, phosphorylation
causing two STATs, not necessarily of the
same type, to form a dimer. This dimer is
able to act as a transcription activator. ‘P'
indicates a phosphate group, PO32-
Figure 12.10. Signal transduction by the MAP
kinase pathway. See the text for details. ‘MK' is
the MAP kinase and ‘P' indicates a phosphate
group, PO32-. Elk-1, c-Myc and SRF (serum
response factor) are examples of transcription
factors activated at the end of the pathway.
Figure 12.11. The Ras signal transduction system. See the text for details.
Abbreviations: GAP, GTPase activating protein; GNRP, guanine nucleotide releasing
protein. ‘P' indicates a phosphate group, PO32-
Figure 12.12. Induction of the calcium second messenger system. See the text for
details. Abbreviations: DAG, 1,2-diacylglycerol; Ins(1,4,5)P3, inositol-1,4,5trisphosphate; PtdIns(4, 5)P2, phosphatidylinositol-4,5-bisphosphate