Fundamentals of Cell Biology
Chapter 12: Control of Gene
Expression
Chapter Summary: The Big Picture (1)
• Chapter foci:
– How the key nuclear signaling proteins enter the
nucleus
– How DNA binding proteins (the effectors of nuclear
signaling pathways) function to control gene
expression
– How changes in gene expression result in changes
in signaling pathways
Chapter Summary: The Big Picture (2)
• Section topics:
– Many signaling proteins enter the nucleus
– Effector proteins in the nucleus are grouped
into three classes
Many signaling proteins enter the nucleus
• Key Concepts (1):
– Numerous classes of cytosolic signaling proteins
routinely pass into and out of the nucleus.
– Proteins that bind to membrane-soluble signaling
molecules move directly into the nucleus and
function as transcription factors.
– Some plasma membrane-associated signaling
proteins and protein fragments enter the nucleus,
but their function in the nucleus is not well
understood.
.
Many signaling proteins enter the nucleus
• Key Concepts (2):
– Nuclear signaling proteins that do not bind DNA
regulate proteins that do.
– The same regulatory mechanisms that control
cytosolic signaling proteins control nuclear signaling
proteins; phosphorylation/dephosphorylation is the
best understood nuclear regulatory mechanism.
Nuclear receptors translocate from the
cytosol to the nucleus during signaling
• Notch is a
transmembrane scaffold
receptor that enters the
nucleus
Figure 12.02: Notch is a cell surface
receptor that signals in the nucleus.
G-protein coupled receptors and GPCR
fragments signal in the nucleus
Table 12.01: GPCRs found in the nucleus.
Figure 12.03: DFZ2 is a GPCR that
signals in the nucleus.
Receptor protein tyrosine kinases
signal in the nucleus
Figure 12.04: Ryk is a tyrosine kinase receptor that signals in the nucleus.
Some protein kinases phosphorylate
nuclear proteins
Figure 12.06: Protein Kinase B
signals in the nucleus.
Figure 12.05: MSKs transmit MAP
kinase signals in the nucleus.
PKC signals in both the cytosol and
nucleus
Other signaling molecules in the
nucleus
• PTEN is a nuclear phosphatase
• An ATP-binding calcium ion channel is present in
the plasma membrane and nuclear envelope in
some neurons
• Adenylyl cyclases are present in the nucleus
Effector proteins in the nucleus are grouped
into three classes
• Key Concepts (1):
– Cohesins hold two DNA strands together by
forming a ring-shaped complex around them.
– Condensins form a ring-shaped structure that
gathers loops of DNA together.
– Histones are phosphorylated by a number of
protein kinases; histone phosphatases remove
them. This modification of histones is critical for
permitting gene expression.
Effector proteins in the nucleus are grouped
into three classes
• Key Concepts (2):
– Histone acetyltransferases add acetyl groups to
histones, thereby loosening their interaction with the
DNA surrounding nucleosomes. This loosening
activates the neighboring DNA by promoting
expression of genes in this area. Histone
deactylases remove the acetyl groups.
– Histone methylation creates a binding site for
heterochromatin proteins and promotes DNA
silencing.
Effector proteins in the nucleus are grouped
into three classes
• Key Concepts (3):
– Histone ubiquitination can either promote transcription or
trigger histone degradation, depending on number of
ubiquitin proteins added to each histone.
– General transcription factors assemble at the core
promoter and serve as the foundation for RNA
polymerase activation.
– Activator and repressor proteins are transcription factors
that control the activity of the general transcription
complex. Some activators bind to enhancer sequences
located hundreds of base pairs away from the core
promoter.
Cohesins and condensins help control
the packaging state of chromatin
Figure 12.07: Cohesins and condensins control the spatial arrangement of chromatin.
Histone modifiers control the structure
of nucleosomes
Figure 12.08: Chromatin modeling is
modification of histones to permit their
removal or sliding along a piece of DNA.
Figure 12.09: Histone modifications on the
nucleosome core particle. Most modified sites
in histones have a single, specific type of
modification, but some sites can have more
than one type of modification.
Acetylation of histones
Figure 12.10: The N-terminal tails of histones H3 and H4 can
be acetylated, methylated, or phosphorylated at several
positions.
Figure 12.11: Acetylation associated with gene
activation occurs by directly modifying specific sites
on histones that are already incorporated into
nucleosomes.
Transcription factors promote the expression
of genes
Figure 12.12: Regulatory regions controlling a gene transcribed by RNA polymerase II.
Figure 12.13: The sequential
assembly of the general
transcription complex for a gene
transcribed by RNA pol II.
How do these proteins find and bind to
this particular region of DNA?
Figure 12.14: Two views of a zinc finger
DNA binding motif.
Figure 12.15: Two views of a leucine zipper.
Enhancer sequences bind activators at a
distance from the promoter
Figure 12.16: Mediator helps form an enormous protein complex near the transcription
start site.
Signal transduction pathways and gene
expression programs form feedback
loops
Figure 12.17: Examples of positive and
negative feedback loops in signal/gene
expression pathways.
Figure 12.18: ERK is a
decision-making protein.