Welcome Each of You to My Molecular Biology Class

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Welcome Each of You to My Molecular Biology Class
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Molecular Biology of the Gene, 5/E --- Watson et
al. (2004)
Part I Chemistry and Genetics Part II
Maintenance of the Genome Part III Expression
of the Genome Part IV Regulation Part V Methods
2005-5-10
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Part IV Regulation
Ch 16 Transcriptional regulation in
prokaryotes Ch 17 Transcriptional regulation in
eukaryotes Ch18 Regulatory RNAs Ch 19 Gene
regulation in development and evolution Ch 20
Genome Analysis and Systems Biology
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Surfing the contents of Part IV --The heart of
the frontier biological disciplines
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• Molecular Biology Course

• Chapter 17
• Gene Regulation
• in Eukaryotes

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• TOPIC 1 Conserved Mechanisms of Transcriptional
  Regulation from Yeast to Human.
• TOPIC 2 Recruitment of Protein Complexes to Genes
  by Eukaryotic Activators.
• TOPIC 3 Transcriptional Repressors
• TOPIC 4 Signal Integration and Combinatorial
  Control.
• TOPIC 5 Signal Transduction and the Control of
  Transcriptional Regulators.
• TOPIC 6 Gene Silencing by Modification of
  Histones and DNA.
• TOPIC 7 Epigenetic Gene Regulation.

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1. Gene Expression is Controlled by Regulatory
Proteins (????)
Principles of Transcription Regulation

• Gene expression is very often controlled by
  Extracellular Signals, which are communicated to
  genes by regulatory proteins
• Positive regulators or activators
  INCREASE the transcription
• Negative regulators or repressors
  
• DECREASE or ELIMINATE the transcription

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• Similarity of regulation between eukaryotes
  and prokaryote
• 1.Principles are the same
• signals (??),
• activators and repressors (?????????)
• recruitment and allostery, cooperative binding
  (??,???????)
• 2. The gene expression steps subjected to
  regulation are similar, and the initiation of
  transcription is the most pervasively regulated
  step.

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• Difference in regulation between eukaryotes and
  prokaryote
• Pre-mRNA splicing adds an important step for
  regulation. (mRNA?????)
• The eukaryotic transcriptional machinery is more
  elaborate than its bacterial counterpart.
  (?????????)
• Nucleosomes and their modifiers influence access
  to genes. (????????)
• Many eukaryotic genes have more regulatory
  binding sites and are controlled by more
  regulatory proteins than are bacterial genes.
  (???????????)

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• A lot more regulator bindings sites in
  multicellular organisms reflects the more
  extensive signal integration

Bacteria
Yeast
Human
Fig. 17-1
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• Enhancer (????) a given site binds regulator
  responsible for activating the gene. Alternative
  enhancer binds different groups of regulators and
  control expression of the same gene at different
  times and places in responsible to different
  signals. Activation at a distance is much more
  common in eukaryotes.
• Insulators (???) or boundary elements (????) are
  regulatory sequences between enhancers and
  promoters. They block activation of a linked
  promoter by activator bound at the enhancer, and
  therefore ensure activators work discriminately.
  

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CHAPTER 17 Gene Regulation in eukaryotes
???????????????? The structure features of the
eukaryotic transcription activators
Topic 1 Conserved Mechanisms of Transcriptional
Regulation from Yeast (??) to Mammals (????)
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• The basic features of gene regulation are the
  same in all eukaryotes, because of the similarity
  in their transcription and nucleosome structure.
• Yeast is the most amenable to both genetic and
  biochemical dissection, and produces much of
  knowledge of the action of the eukaryotic
  repressor and activator.
• The typical eukaryotic activators works in a
  manner similar to the simplest bacterial case.
• Repressors work in a variety of ways.

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• 1. Eukaryotic activators (??????) have separate
  DNA binding and activating functions???????,
  which are very often on separate domains of the
  protein.

Fig. 17-2 Gal4 bound to its site on DNA
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• Eukaryotic activators---Example 1 Gal4
• Gal4 is the most studied eukaryotic activator
• Gal4 activates transcription of the galactose
  genes in the yeast S. cerevisae.
• Gal4 binds to four sites (UASG) upstream of GAL1,
  and activates transcription 1,000-fold in the
  presence of galactose

Fig. 17-3 The regulatory sequences of the Yeast
GAL1 gene.
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• Eukaryotic activators---Example 1 Gal4
• Experimental evidences showing that Gal4 contains
  separate DNA binding and activating domains.
• Expression of the N-terminal region (DNA-binding
  domain) of the activator produces a protein bound
  to the DNA normally but did not activate
  transcription.
• Fusion of the C-terminal region (activation
  domain) of the activator to the DNA binding
  domain of a bacterial repressor, LexA activates
  the transcription of the reporter gene. Domain
  swap experiment

??????1-Experiment introduction series
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• Domain swap experiment
• Moving domains among proteins, proving that
  domains can be dissected into separate parts of
  the proteins.
• Many similar experiments shows that DNA binding
  domains and activating regions are separable.

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• Box 1 The two hybrid Assay (?????) is used to
  identify proteins interacting with each other.
  (??????2)

Fuse protein A and protein B genes to the DNA
binding domain and activating region of Gal4,
respectively.
Produce fusion proteins
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• 2. Eukaryotic regulators use a range of DNA
  binding domains, but DNA recognition involves the
  same principles as found in bacteria.
• Homeodomain proteins
• Zinc containing DNA-binding domain zinc finger
  and zinc cluster
• Leucine zipper motif
• Helix-Loop-Helix proteins basic zipper and HLH
  proteins

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• Bacterial regulatory proteins
• Most use the helix-turn-helix motif to bind DNA
  target
• Most bind as dimers to DNA sequence each monomer
  inserts an a helix into the major groove.
• Eukaryotic regulatory proteins
• Recognize the DNA using the similar principles,
  with some variations in detail.
• In addition to form homodimers (?????), some form
  heterodimers (?????) to recognize DNA, extending
  the range of DNA-binding specificity.

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• Homeodomain proteins The homeodomain (?????) is
  a class of helix-turn-helix DNA-binding domain
  and recognizes DNA in essentially the same way as
  those bacterial proteins.

What is the same?
Figure 17-5
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Zinc containing DNA-binding domains (?????) Zinc
finger proteins (TFIIIA) and Zinc cluster domain
(Gal4)
Figure 17-6
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Leucine Zipper Motif (???????) The Motif
combines dimerization and DNA-binding surfaces
within a single structural unit.
Figure 17-7
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Dimerization (???) is mediated by hydrophobic
interactions between the appropriately-spaced
leucine (???) to form a coiled coil structure
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(No Transcript)
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Helix-Loop-Helix motif similar as in leucine
zipper motif.
Figure 17-8
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myogenic factor??????????????
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Because the region of the a-helix that binds DNA
contains baisc amino acids residues, Leucine
zipper and HLH proteins are often called basic
zipper and basic HLH proteins. Both of these
proteins use hydrophobic amino acid residues for
dimerization.
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• 3. Activating regions (????) are not well-defined
  structures

• The activating regions are grouped on the basis
  of amino acids content.
• Acidic activation region (??????) contain both
  critical acidic amino acids and hydrophobic
  acids.yeast Gal4
• Glutamine-rich region (???????) mammalian
  activator SP1
• Proline-rich region (??????) mammalian
  activator CTF1

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CHAPTER 17 Gene Regulation in eukaryotes
???????????????????????? Activation of the
eukaryotic transcription by recruitment
Activation at a distance
Topic 2 Recruitment of Protein Complexes to
Genes by Eukaryotic Activators
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• Eukaryotic activators (??????) also work by
  recruiting (??) as in bacteria, but recruit
  polymerase indirectly in two ways
• 1. Interacting with parts of the
• transcription machinery.
• 2. Recruiting nucleosome modifiers that alter
  chromatin in the vicinity of a gene.

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1. Activators recruit the transcription machinery
to the gene.
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• The eukaryotic transcriptional machinery contains
  polymerase and numerous proteins being organized
  to several complexes, such as the Mediator and
  the TF?D complex. Activators interact with one or
  more of these complexes and recruit them to the
  gene.

Figure 17-9
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• Box 2 Chromatin Immuno-precipitation (ChIP)
  (????????) to visualize where a given protein
  (activator) is bound in the genome of a living
  cell.) (??????3)

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• Activator Bypass Experiment (???????)-Activation
  of transcription through direct tethering of
  mediator to DNA. (??????4)

Directly fuse the bacterial DNA-binding protein
LexA protein to Gal11, a component of the
mediator complex to activate GAL1 expression.
Figure 17-10
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At most genes, the transcription machinery is not
prebound, and appear at the promoter only upon
activation. Thus, no allosteric activation of the
prebound polymerase has been evident in
eukaryotic regulation?
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2. Activators also recruit modifiers that help
the transcription machinery bind at the promoter

• Two types of Nucleosome modifiers
• Those add chemical groups to the tails of
  histones (???????????), such as histone acetyl
  transferases (HATs)
• Those remodel the nucleosomes (?????), such as
  the ATP-dependent activity of SWI/SNF.

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• How the nucleosome modification help activate a
  gene?
• Loosen the chromatin structure by chromosome
  remodeling (Fig. 17-11b) and histone modification
  such as acetylation (Fig. 17-11a), which uncover
  DNA-binding sites that would otherwise remain
  inaccessible within the nucleosome.

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(???????)
uncover DNA-binding sites

• Fig 17-11 Local alterations in chromatin directed
  by activators

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• 2. Adding acetyl groups to histones helps the
  binding of the transcriptional machinery. One
  component of TFIID complex bears bromodomains
  that specifically bind to the acetyl groups.
  Therefore, a gene bearing acetylated nucleosomes
  at its promoter have a higher affinity for the
  transcriptional machinery than the one with
  unacetylated nucleosomes.

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???????
One component of TFIID complex bears bromodomains.
Figure 7-39 Effect of histone tail modification
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3. Action at a distance loops and insulators

• Many enkaryotic activators-particularly
• in higher eukaryotes-work from a distance.
• How?
• Some proteins help, for example Chip protein in
  Drosophila.
• The compacted chromosome structure help. DNA is
  wrapped in nucleosomes in eukaryotes. So sites
  separated by many base pairs may not be as far
  apart in the cell as thought.

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Specific cis-acting elements called insulators
(???) control the actions of activators,
preventing the activating the non-specific genes
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• Insulators
• block
• activation
• by
• enhancers

Figure 17-12
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• Transcriptional Silencing (????)
• Transcriptional Silencing is a specialized form
  of repression that can spread along chromatin,
  switching off multiple genes without the need for
  each to bear binding sites for specific
  repressor.
• Insulator elements (?????) can block this
  spreading, so insulators protect genes from both
  indiscriminate activation and repression.????????
  ?????
• ApplicationA gene inserted at random into the
  mammalian genome is often silenced, and placing
  insulators upstream and downstream of that gene
  can protect the gene from silencing.

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• 4 Appropriate regulation of some groups of genes
  requires locus control region (LCR).

1. Human and mouse globin genes are clustered in
   genome and differently expressed at different
   stages of development
2. A group of regulatory elements collectively
   called the locus control region (LCR), is found
   30-50 kb upstream of the cluster of globin genes.
   It binds regulatory proteins that cause the
   chromatin structure to open up, allowing access
   to the array of regulators that control
   expression of the individual genes in a defined
   order.

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Figure 17-13
Please compare LCR with the Lac operon controlled
gene expression in bacteria
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• Another group of mouse genes whose expression
  is regulated in a temporarily and spatially
  ordered sequence are called HoxD genes. They are
  controlled by an element called the GCR (global
  control region) in a manner very like that of LCR.

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CHAPTER 17 Gene Regulation in eukaryotes
??????????(?????)????
Topic 3 Transcriptional Repressor its
regulation
In eukaryotes, most repressors do not repress
transcription by binding to sites that overlap
with the promoter and thus block binding of
polymerase. (Bacteria often do so)
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• Commonly, eukaryotic repressors recruit
  nucleosome modifiers that compact the nucleosome
  or remove the groups recognized by the
  transcriptional machinery contrast to the
  activator recruited nucleosome modifers, histone
  deacetylases (????????) removing the acetyl
  groups. Some modifier adds methyl groups to the
  histone tails, which frequently repress the
  transcription.
• This modification causes transcriptional
  silencing.

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• Three other ways in which an eukaryotic repressor
  works include
• Competes with the activator for an overlapped
  binding site.
• Binds to a site different from that of the
  activator, but physically interacts with an
  activator and thus block its activating region.
• Binds to a site upstream of the promoter,
  physically interacts with the transcription
  machinery at the promoter to inhibit
  transcription initiation.

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Competes for the activator binding
Inhibits the function of the activator.
Figure 17-19 Ways in which eukaryotic repressor
work
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Binds to the transcription machinery
Recruits nucleosome modifiers (most common)
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• A specific example Repression of the GAL1 gene
  in yeast

In the presence of glucose, Mig1 binds to a site
between the USAG and the GAL1 promoter, and
recruits the Tup1 repressing complex. Tup1
recruits histone deacetylases, and also directly
interacts with the transcription machinery to
repress transcription.
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CHAPTER 17 Gene Regulation in eukaryotes
???????????????????? Features of the eukaryotic
transcriptional regulation signal integration
and combinatorial control
Topic 4 Signal Integration and Combinatorial
Control
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1. Activators work together synergistically (???)
to integrate signals.
???????????????
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Review the Lac operon control in bacteria. Two
signals are integrated to control Lac expression
Glucose
Lactose
Figure 16-6
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• In multicellular organisms, signal integration
  (????) is used extensively. In some cases,
  numerous signals are required to switch a gene
  on. However, each signal is transmitted to the
  gene by a separate regulator, and therefore,
  multiple activators often work together, and they
  do so synergistically (two activators working
  together is greater than the sum of each of them
  working alone.)

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Three strategies of the synergy (???????) S1
Multiple activators recruit a single component of
the transcriptional machinery. For example, by
touching the different part of the mediator
complex (??????). The combined binding energy has
an exponential effect on recruitment. S2
Multiple activators each recruit a different
component of the transcriptional machinery. These
components binds to the promoter DNA
inefficiently without help.
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S3 Multiple activators help each other bind to
their sites upstream of the gene they control.
(Figure 17-14)
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• a.Classical cooperative binding.
• b. Both proteins interacting with a third
  protein.
• c. The first protein recruit a nucleosome
  remodeller whose action reveal a binding site for
  the second protein.
• d. Binding a protein unwinds the DNA from
  nucleosome a little, revealing the binding site
  for another protein.

Figure 17-14 Cooperative binding of activators
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2. Signal integration the HO gene is controlled
by two regulators one recruits nucleosome
modifiers and the other recruits mediator.
S3???example
The HO gene is only expressed in mother cells and
only a certain point in the cell cycle, resulting
in the budding division feature of yeast S.
cerevisiae (????). The mother cell and cell cycle
conditions (signals) are communicated to the HO
gene (target) by two activators SWI5 and SBF
(communicators).
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• SWI5 acts only in the mother cell and binds to
  multiple sites some distance from the gene
  unaided, which recruit enzymes to open the SBF
  binding sites.
• SBF only active at the correct stages of the
  cell cycle, and cannot bind the sites unaided.

(??? ????)
Alter the nucleosome
Figure 17-15
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Figure 17-14 Cooperative binding of activators.
(c) The first protein recruit a nucleosome
remodeller whose action reveal a binding site for
the second protein.
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3. Signal integration Cooperative binding of
activators at the human b-interferon gene.
S3???example
The human b-interferon gene (target gene) is
activated in cells upon viral infection (signal).
Infection triggers three activators
(communicator) NFkB, IRF, and Jun/ATF.
Activators bind cooperatively to sites adjacent
to one another within an enhancer located about 1
kb upstream of the promoter, which forms a
structure called enhanceosome.
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(??b?????)

1. Activators interact with each other
2. HMG-I binds within the enhancer and aids the
   binding of the activators (bends the DNA to
   promote the activator interaction)

Figure 17-16
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HMG-I is constitutively active in the cells, and
play an architectural role in the INF-b gene
activation process.
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Figure 17-14 Cooperative binding of activators.
(a)Classical cooperative binding through direct
interaction between the two proteins.
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4. Combinatory control (????) lies at the heart
of the complexity and diversity of eukaryotes, in
which Both activators and repressors work
together.
?????????????????????????????????????????,????????
???????
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Page 499 Slide 47 in Ch 16
Review
7 Combinatorial Control (????) CAP controls
other genes as well

• A regulator (CAP) works together with different
  repressors at different genes, this is an example
  of Combinatorial Control.
• In fact, CAP acts at more than 100 genes in
  E.coli, working with an array of partners.

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There is extensive combinatorial control in
eukaryotes.---A generic picture
Four signals
Figure 17-18
Three signals
In complex multicellular organisms, combinatorial
control involves many more regulators and genes
than shown above. Both activators and repressors
can be involved.
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5. An example combinatory control of the
mating-type genes from S. cerevisiae
(?????????????)
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• The yeast S. cerevisiae exists in three forms
• ---two haploid cells (???) of different mating
  types- a and a.
• ---the diploid cells (???) (a/a) formed when an a
  and an a cell mate
• and fuse.
• Cells of the two mating types (a and a) differ
  because they express different sets of genes a
  specific genes and a specific genes.

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• a cells make the regulatory protein a1,
• a cells make the protein a1 and a2.
• Both cell types express the fourth regulator
  protein Mcm1 that is also involved in regulatory
  the mating-type specific genes.
• How do these regulators work together to keep a
  cell in its own type? Figure 17-19

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Figure 17-19 Control of cell-type specific genes
in yeast
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CHAPTER 17 Gene Regulation in eukaryotes
??????????????????? Signal transduction---A life
science frontier centered on the eukaryotic
transcriptional regulation.
Topic 5 Signal Transduction (????) and the
Control of Transcriptional Regulators
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Topic 4 Signal Transduction and the Control of
Transcriptional Regulators
1. Signals are often communicated to
transcriptional regulators through signal
transduction pathway
??????????????????????
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• Environmental Signals/Information (??)
• 1. Small molecules such as sugar, histamine
  (??).
• 2. Proteins released by one cell and received by
  another.
• In eukaryotic cells, most signals are
  communicated to genes through signal transduction
  pathway (indirect), in which the initiating
  ligand is detected by a specific cell surface
  receptor.
• What about in bacteria?

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Signal transduction pathway
1. The initial ligand (signal) binds to an
extracellular domain of a specific cell surface
receptor
2. The signal is thus communicated to the
intracellular domain of receptor (via an
allosteric change or dimerization )

• 3. The signal is then relayed (????) to the
  relevant transcriptional regulator.

4. The transcriptional regulator control the
target gene expression (topic 2-4).
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• a. The STAT pathway

b. The MAP kinase pathway
Figure 17-22Signal transduction pathway
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Topic 4 Signal Transduction and the Control of
Transcriptional Regulators
2. Signals control the activities of eukaryotic
transcriptional regulators in a variety of
ways---The mechanisms of signal transduction.
????????????????????????????
In eukaryotes, a signal can be communicated,
directly or indirectly, to a transcriptional
regulator.
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• Mechanism 1 unmasking an activating region
  (Topic 2 3)
• A conformational change to reveal the previously
  buried activating region.
• Releasing of the previously bound masking
  protein. Example the activator Gal4 is
  controlled by the masking Gal80) (Fig.17-23).
• Some masking proteins not only block the
  activating region of an activator but also
  recruit a deacetylase enzyme to repress the
  target genes. Example Rb represses the function
  of the mammalian transcription activator E2F in
  this way. Phosphorylation of Rb releases E2F to
  activate the target gene expression.

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• Activator Gal4 is regulated by a masking protein
  Gal80

Gal4
Figure 17-23
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• Mechanism 2 Transport into and out of the
  nucleus (Fig.17-21)
• When not active, many activators and repressors
  are held in the cytoplasm. The signaling ligand
  causes them to move into the nucleus where they
  activate transcription (Fig.19-4b).

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• Other Mechanisms 1 A cascade of kinases that
  ultimately cause the phosphorylation of regulator
  in nucleus (new) (Fig.19-4a).

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• Other Mechanisms 2 The activated receptor is
  cleaved by cellular proteases (???), and the
  c-terminal portion of the receptor enters the
  nuclease and activates the regulator
  (new)(Fig.19-4c).

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CHAPTER 17 Gene Regulation in eukaryotes
Topic 6 Gene Silencing by Modification of
Histones and DNA
88

• Transcriptional silencing is a position effect.
  (1) A gene is silenced because of where it is
  located, not in response to a specific
  environmental signal. (2) Silencing can spread
  over large stretches of DNA, switching off
  multiple genes, even those quite distant from the
  initiating event.

89

• The most common form of silencing is associated
  with a dense form of chromatin called
  heterochromatin.
• Heterochromatin is frequently associated with
  particular regions of the chromosome, notably the
  telomeres, and the centromeres.
• In mammalian cells, about 50 of the genome is
  estimated to be in some form of heterochromatin.

90

• Transcriptional silencing is associated with
  Modification of nucleosomes that alters the
  accessibility of a gene to the transcriptional
  machinery and other regulatory proteins.
• The modification enzymes for silencing include
  deacetylases, DNA methylases.

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Topic 6 Gene Silencing by Modification of
Histones and DNA
6-1. Silencing in yeast is mediated by
deacetylation and methylation of the histones
??????????????????????????
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• The telomeres, the silent mating-type locus, and
  the rDNA genes are all silent regions in S.
  cerevisiae.
• Three genes encoding regulators of silencing,
  SIR2, 3, and 4 have been found (SIR stands for
  Silent Information Regulator).

Rap1 recruits Sir complex to the temomere. Sir2
deacetylates nearby nucleosome.
Fig. 17-24. Silencing at the yeast telomere
93
Silencing specificity is determined by Rap1, the
telomere DNA-binding protein. It can also be
determined by RNA molecules using RNAi machinery
(Chapter 18). The spreading of silencing is
restricted/controlled by insulators and other
kind of histone modifications that block binding
of the Sir2 proteins.
94

• Transcription can also be silenced by methylation
  of DNA by histone methyltransferase (H3 and H4,
  Chapter 7).
• This enzyme have been recently found in yeast,
  but is common in mammalian cells. Its function is
  better understood in higher eukaryotes.
• In higher eukaryotes, silencing is typically
  associated with chromatin containing histones
  that both deacetylated and methylated.

95
Topic 6 Gene Silencing by Modification of
Histones and DNA
6-2. In Drosophila, HP1 recognizes Methylated
Histones and Condense Chromatin.
????,HP1???????????????????
96

• HP1 protein is a component of heterochromatin in
  Drosophila that binds to methylated residue in
  histone H3.
• Such a histone modification is produced by
  Su(Var)3-9.
• Different types of modification at the histones
  can be involved in distinct geene regulation.
  What will happen when multiple forms of
  modification occur? ---A Histone Code
  hypothesis.

97

• Box 17-4 Is there a histone code?
• According to this idea, different patterns of
  modification on histone tails can be read to
  mean different things. The meaning would be the
  result of the direct effects of these
  modifications on chromatin density and form.
• But in addition, the particular pattern of
  modifications at any given location would recruit
  specific proteins.

98
Topic 6 Gene Silencing by Modification of
Histones and DNA
6-3. DNA Methylation Is Associated with Silenced
Genes in Mammlian cells.
DNA?????????????????????DNA????????????
Some mammalian genes are kept silent by
methylation of nearby DNA sequences.
99

• Large regions of mammalian genome are marked by
  methylation of DNA sequences, which is often seen
  in heterochromatic regions. Why?
• The methylated DNA sequences are often
• recognized by DNA-binding proteins (such as
  MeCP2) that recruit histone decetylases and
  histone methylases, which then modify nearby
  chromatin.
• Thus, methylation of DNA can mark sites where
  heterochromatin subsequently forms (Fig. 17-25).

100
Fig. 17-25 Switching a gene off through DNA
methylation and the subsequent histone
modification
101

• DNA methylation lies at the heart of Imprinting
• Imprinting- in a diploid cell, one copy of a gene
  from the father or mother is expressed while the
  other copy is silenced.
• Two well-studied examples human H19 and
  insulin-like growth factor 2 (Igf2) genes.

102
Enhancer activate both gene transcription ICR
an insulator binds CTCF protein and blocks the
activity of the enhancer on Igf2.Methylation of
ICR allows the enhancer to activate Igf2. H19
repression is mediated by DNA methylation and the
subsequent MeCP2 binding to the methylated ICR
Figure 17-26 Imprinting
103
CHAPTER 17 Gene Regulation in eukaryotes
Topic 7 Epigenetic Regulation
104

• Patterns of gene expression must
• sometimes be inherited.
• After the expression of specific genes in a set
  of cells are switched on by a signal, these
  genes may have to remain switched on for many
  cell generations, even if the signal that induced
  them is present only fleetingly (???).
• The inheritance of gene expression patterns, in
  the absence of both mutation and the initiating
  signal, is called epigenetic regulation.

105
Topic 7 Epigenetic Regulation
7-1. Some States of Gene Expression Are Inherited
through Cell Division Even When the Initiating
Signal Is No Longer Present
????????????????????????????
The maintenance of a bacteriophage l lysogen is
an example of epigenetic regulation. Figure
17-27
106

• Establishment of lysogeny synthesis of the
  essential lysogenic l repressor is established by
  transcription from one promoter and then
  maintained by transcription from another one.

107

• DNA methylation provides a mechanism of
  epigenetic regulation. DNA methylation is
  reliably inherited throughout cell division Fig.
  17-28.
• Certain DNA methylases can methylate, at low
  frequency, previously unmodified DNA but far
  more efficiently, the so-called maintenance
  methylases modify hemimethylated DNA-the very
  substrate provided by replication of fully
  methylated DNA.
• A link with reprogramming of somatic cells into
  Embryonic Stem-like cells. Box 17-6

108

• Figure 17-28 Patterns of DNA methylation can be
  maintained through cell division

109
Key points of the chapter

• The structure features of the eukaryotic
  transcription activators.
• Activation of the eukaryotic transcription by
  recruitment Activation at a distance.
• Transcriptional repressor its regulation
• Signal integration and combinatorial control
• Signal transduction communicating the signals to
  transcriptional regulators.
• Gene silencing and Epigenetic regulation.
• 7. 4 experimental methods introduced (yeast
  two-hybrid and ChIP).