School of Biotechnology,

International University
Email: bhthuy@hcmiu.edu.vn

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OUTLINES

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OUTLINES

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 Evidence that DNA is the genetic material

ØA model of genetic
inheritance was in place
in the early 1900s:
• Mendel’s “laws” of genetics
– inherit one copy of each
gene from each parent
• Chromosomes as
locations/carriers of genes
• Distribution of chromosomes
in making sex cells explains
Mendel’s laws

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 Evidence that DNA is the genetic material:
DNA is required for genetic
transformation of bacteria
Ø Studies by Griffith in the
1920s of pneumococcus
in mice
• Smooth (S) strain killed mice,
rough (R) strain did not
• Heat-killed S strain did not
kill mice, but heat-killed S +
R strain killed mice
• Some “transforming principle”
from the heat-killed S strain
changed the R strain to
make it deadly
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 The search for the genetic material
• 1928, Fred Griffith worked with virulent S and
nonvirulent R strain Pneumoccocus bacteria
• 1944, Avery and colleagues announced that the
transforming agent was DNA.
• 1952, Hershey and Chase experiments on
bacteriophage

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 Evidence that DNA is the genetic material

• Viruses inject DNA into bacteria and take them

over: the Hershey-Chase experiments
– viruses that infect bacteria are called
bacteriophages (shortened as phages)
– viruses execute a “genetic takeover” of cells

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EXPERIMENT
Is protein or DNA the genetic material of phage T2?
Alfred Hershey and Martha Chase used radioactive sulfur and phosphorus to trace the
fates of the protein and DNA, respectively, of T2 phages that infected bacterial cells.
1 2 3 4
Mixed radioactively Agitated in a blender to Centrifuged the mixture Measured the
labeled phages with separate phages outside so that bacteria formed radioactivity in
bacteria. The phages the bacteria from the a pellet at the bottom of the pellet and
infected the bacterial cells. bacterial cells. the test tube. the liquid

Radioactive Empty Radioactivity

Phage protein protein shell (phage protein)
in liquid
Bacterial cell

Batch 1: Phages were

DNA
grown with radioactive Phage
sulfur (35S), which was DNA
incorporated into phage Centrifuge
protein (pink).
Radioactive
DNA Pellet (bacterial
cells and contents)
Batch 2: Phages were
grown with radioactive
phosphorus (32P), which
was incorporated into
phage DNA (blue).
Centrifuge
Radioactivity
RESULTS (phage DNA)
Pellet in pellet
Phage proteins remained outside the bacterial cells during infection, while phage DNA entered the
cells. When cultured, bacterial cells with radioactive phage DNA released new phages with some
radioactive phosphorus.
CONCLUSION
DNA, not protein, functions as the T2 phage’s genetic material. 8
 Evidence that DNA is the genetic material
• Prior to the 1950s, it was already known that DNA
– Is a polymer of nucleotides, each consisting of
three components: a nitrogenous base, a sugar,
and a phosphate group
Sugar-phosphate Nitrogenous
backbone bases
5 end CH3
O– 5
O P O CH2 H O
O 1
O– 4 H H N N
H H
H
3 2 O
H Thymine (T)
O
H H
O P O CH2 N
O N
O– H H N H
H H N
N
H
H
Adenine (A)
O H H
O P O CH2 H N H
O
O– H H N N
H H
H O
Cytosine (C)
O 5
O P O CH2 H N
O 1 O
O– 4 H H N
Phosphate H H
2 N H
3 N DNA nucleotide
OH H
Sugar (deoxyribose) N H
H
Figure 16.5 3 end Guanine (G)
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Structure of DNA:
the double helix
Ø X-ray diffraction
studies by Rosalind
Franklin and
Maurice Wilkins
indicated a helical
molecule
• molecule has three
repeating patterns
that any model of its
structure must
account for
• the data indicated a
helix

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• Maurice Wilkins and Rosalind Franklin
– Were using a technique called X-ray
crystallography to study molecular structure
• Rosalind Franklin
– Produced a picture of the DNA molecule using this
technique

(a) Rosalind Franklin (b) Franklin’s X-ray diffraction

Figure 16.6 a, b Photograph of DNA
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• Watson and Crick deduced that DNA was a
double helix
– Through observations of the X-ray crystallographic
images of DNA
G C
A T
T A

1 nm

G C
3.4 nm
C G
A T
C G

T A

T A
A T

A T

G C
0.34 nm
A T

Figure 16.7a, c (a) Key features of DNA structure (c) Space-filling model

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Structure of DNA: the double helix

Ø The accepted model for the structure of the DNA double

helix was published by James Watson and Francis Crick
in 1953
Ø DNA was envisioned as a twisted ladder, with the sugar-
phosphate backbone forming the sides and basepairs
forming the rungs 13
Structure of DNA: the double helix
Ø Model explained all three
repeating patterns seen
in x-ray diffraction, as
well Chargaff’s data on
base ratios
Ø Double helix with
antiparallel strands
Ø Each strand a nucleotide
chain held together by
phosphodiester linkages
Ø Strands held together by
hydrogen bonds between
the bases (basepairs)
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Structure of DNA: the double helix
Ø Strands held together by hydrogen
bonds between the bases
(basepairs)
• C paired with G, with 3
hydrogen bonds predicted
• A paired with T, with 2 hydrogen
bonds predicted
Ø Described as complementary
strands
Ø Model strongly suggested a way to
store information in the sequence
of bases, which indeed appears to
be true
Ø The determination of the DNA
structure by Watson and Crick is
considered the major landmark of
modern biology 15
 The Basic Principle: Base Pairing
to a Template Strand
• In DNA replication
– The parent molecule unwinds, and two new
daughter strands are built based on base-pairing
rules
T
A T A T A A T A T A T
C G C G C G C G C G C G
T A T A T A T A T A T A
A T A T A T A T A T A T
G C G C G C C G C G C
G

(a) The parent molecule has two
complementary strands of DNA.
Each base is paired by hydrogen
bonding with its specific partner,
A with T and G with C.
(b) The first step in replication is
separation of the two DNA
strands.
(c) Each parental strand now (d) The nucleotides are connected
serves as a template that to form the sugar-phosphate
determines the order of backbones of the new strands.
nucleotides along a new, Each “daughter” DNA
complementary strand. molecule consists of one parental
strand and one new strand.

Figure 16.9 a–d

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 DNA replication
Ø The replication process overview
– DNA replication requires the coordinated
activity of many enzymes and other
proteins
– Also requires the presence of nucleotide
triphosphates

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 DNA replication
Origins of replication
• DNA replication begins at specific sites
– Synthesis generally proceeds in both directions
from an origin, creating a “replication bubble”
– There is usually only one origin of replication in
the circular bacterial DNA
– Eukaryotic chromosomes usually have several
origins of replication each
• Both strands are replicated at the same time on
both sides of the replication bubble, producing Y-
shaped replication forks that move as synthesis
proceeds

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DNA replication

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 Elongating a New DNA Strand
• Elongation of new DNA at a replication fork
– Is catalyzed by enzymes called DNA
polymerases, which add nucleotides to the 3
end of a growing strand
New strand Template strand
5 end 3 end 5 end 3 end

Sugar A T A T
Phosphate Base

C G C G

G C G C

A T A
T OH
P P P
P
P C Pyrophosphate 3 end C
OH
2 P
Nucleoside
Figure 16.13 triphosphate 5 end 5 end
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 DNA replication
Ø Unwinding and opening DNA
• The twisted double helix must be unwound and the basepair
bonds broken (“opening” the DNA molecule)
• DNA helicase does the unwinding and opening
• Single-strand DNA binding proteins keep it open
• Topoisomerases break and rejoin strands, resolving knots
and strains that occur

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 DNA replication
Ø Direction of synthesis
• DNA polymerases direct synthesis of new strands
• synthesis proceeds by adding nucleotides onto the 3’ end
of a strand
• Thus, synthesis can only proceed in the 5’  3’ direction
• The nucleotide added is from a deoxynucleotide
triphosphate; two phosphates are released in the process
– energy to drive the reaction comes from these

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 DNA replication
ØPriming new strands
– DNA polymerase can only add onto an existing strand,
so it can’t start the strand
– Primase starts the strand by making an RNA primer
that is a few (usually ~10) ribonucleotides long
– DNA polymerase can then add nucleotides starting at
the end of the RNA primer
– The RNA primer is later degraded and (usually)
replaced with DNA

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 DNA replication
Ø Leading and lagging strands
– The 5’  3’ directionality of synthesis complicates the
replication activity
– One strand being synthesized, the leading strand,
has its 3’ end at the fork; thus, its synthesis can
proceed continuously, in the direction that the fork
moves
– The other, lagging strand has its 5’ end at the fork; it
must be synthesized in the “opposite direction” from
the leading strand

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• the lagging strand is thus made in
short (100-1000 nt) Okazaki
fragments

• fragments are later connected by

DNA ligase

• DNA ligase also joins together

DNA strands when replication
forks meet
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 A summary of DNA replication
1 Primase joins RNA nucleotides
into a primer. 3 5
5 3
Template
2 DNA pol III adds DNA nucleotides to the
strand primer, forming an Okazaki fragment.
3 RNA primer 3 5
5 1
3 After reaching the next
RNA primer (not shown),
DNA pol III falls off. Okazaki
3
3 fragment5
1
5
4 After the second fragment is
primed. DNA pol III adds DNA
nucleotides until it reaches the
5 off.
first primer and falls 3
3 2 5
1

5 DNA pol 1 replaces the

RNA with DNA, adding to
the 3 end of fragment 2.
5 3
3 2 5
1

6 DNA ligase forms a bond 7 The lagging strand

between the newest DNA in this region is now
and the adjacent DNA of complete.
fragment 1. 5 3
3 2 5
1

Figure 16.15
Overall direction of replication 26
 DNA replication
• DNA proofreading and DNA
repair
– DNA polymerase proofreads:
initial error rate about 1 in
100,000; final rate about 1 in
100,000,000 (1 in 108)
– cells have DNA repair
mechanisms to fix most
mistakes that get through as
well as to fix most damaged
DNA

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 DNA replication
ØThe dead end: problem
at the telomeres
– The ends of chromosomes
are called telomeres
– They present special
problems for DNA
replication: the 5’ end RNA
primer cannot be replaced
with DNA, creating 5’ end
gaps
– This leads to shorting of
chromosomes at the ends
with each cell generation
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 DNA replication
ØThe dead end: problem at the telomeres
v In some cells, special telomerase enzymes can
generate longer telomeres
• Telomerase is required in germ-line cells
• Telomerase is active in cancer cells as well

1 µm
Eukaryotes have repetitive, noncoding sequences called
telomeres at the ends of their DNA
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A Chromosome consists of a DNA molecule
packed together with proteins

DNA packaging
The DNA molecule is too long if not folded

– Bacteria have much less DNA in their cells than eukaryotes

do, but even so the length of their DNA molecule if
stretched out would be 1000x the length of the cell itself
– Thus, even in the bacteria DNA must be “packaged”, folded
and coiled to make it fit in the cell
– Eukaryotes have even more DNA, and use somewhat
elaborate means to package the DNA even when it is in
“decondensed” chromatin

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 DNA packaging
Ø Nucleosomes are the main
packaging mechanism for
eukaryotic DNA
Ø The nucleosome is made up of
8 protein subunits, acting like
a “spool” for the DNA “thread”
Ø The proteins are called
histones
Ø Histones are positively
charged, and thus able to
associate with the negatively
charged phosphates of the
DNA backbone
Ø The 8 proteins in a
nucleosomes are 2 each of 4
different histones
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 DNA packaging
• further packaging: histone
H1 and scaffolding
proteins
– 30 nm fibers form looped
domains that are ~300
nm wide and attached to
non-histone scaffolding
proteins
• this level of packing is
found only for some
regions of DNA, except
when chromosomes are
condensed for cell
division

– the next step connects

looped domains into an
~700 nm fiber that is
considered fully
condensed chromatin 32
OUTLINES

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 Genes generally are information for
making specific proteins
Ø In connection with the rediscovery of Mendel’s work
around the dawn of the 20th century, the idea that
genes are responsible for making enzymes was
advanced
Ø This view was summarized in the classic work Inborn
Errors of Metabolism (Garrod 1908)

Premise: Certain diseases

arise from metabolic
disorders

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Genes generally are information for
making specific proteins

• Work by Beadle and Tatum in the

1940s refined this concept
– found mutant genes in the fungus
Neurospora that each affected a
single step in a metabolic pathway
– developed the “one gene, one
enzyme” hypothesis
• Follow-up work by Srb and Horowitz
illustrated this even more clearly (their
work is actually what is presented in
your textbook and in the figure here)

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 Genes generally are information for
making specific proteins

ØLater work by Pauling and others showed

that other proteins are also generated
genetically
ØAlso, some proteins have multiple
subunits encoded by different genes
ØThis ultimately led to the “one gene, one
polypeptide” hypothesis

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 RNA
ØRNA has some structural
distinctions from DNA
• Typically single-stranded
(although often with folds and
complex 3D structure)
• Sugar is ribose; thus, RNA
polymers are built from
ribonucleotides
ü -OH at the #2 C on the ribose, vs.
deoxyribose in DNA
• Uracil (U) functions in place of T

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 RNA (ribonucleic acid)
Ø Three main forms of RNA are used: mRNA,
tRNA, and rRNA
• mRNA or messenger RNA: copies the actual
instructions from the gene
• tRNA or transfer RNA: links with amino acids and bring
them to the appropriate sites for incorporation in
proteins
• rRNA or ribosomal RNA: main structural and catalytic
components of ribosomes, where proteins are actually
produced
• All are synthesized from DNA templates (thus, some
genes code for tRNA and rRNA, not protein)

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• DNA  RNA is transcription
– making RNA using directions from a
DNA template
– transcribe = copy in the same language
(language used here is base sequence)

• RNA  protein is translation

– making a polypeptide chain using
directions in mRNA
– translate = copy into a different
language; here the translation is from
base sequence to amino acid sequence

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Srb and Horowitz further characterize the mutant surviving
arginine suplemented medium to investigate the arginine
synthesis pathway

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 Conclusions

• Ornithine -> Citrullin -> Arginine

• One gene – one enzyme 41
 Transcription (DNA  RNA)

• Transcription is the synthesis of RNA using

information in the DNA.
• The two nucleic acids are written in different forms
of the same language, and the information is
simply transcribed, or “rewritten” from DNA to
RNA
• RNA molecule is called messenger RNA (mRNA)
because it carries a genetic message from the
DNA to the protein-synthesizing machinery of the
cell.
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 Translation
• Is the synthesis of a polypeptide using the
information in the mRNA.
• During this stage, there is a change in
language: The cell must translate the
nucleotide sequence of an mRNA molecule into
the amino acid sequence of a polypeptide.
• The sites of translation are ribosomes,
complex particles that facilitate the orderly
linking of amino acids into polypeptide chains
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Overview: the roles of transcription
and translation in the flow of genetic
information

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45
Central Dogma of Gene Expression
DNA  RNA  protein

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 Transcription (DNA  RNA)
ØRNA is synthesized as a complementary strand
using DNA-dependent RNA polymerases
– Process is somewhat similar to DNA synthesis, but
no primer is needed
– Bacterial cells each only have one type of RNA
polymerase
– Eukaryotic cells have three major types of RNA
polymerase
• RNA polymerase I is used in making rRNA
• RNA polymerase II is used in making mRNA and
some small RNA molecules
• RNA polymerase III is used in making tRNA and
some small RNA molecules
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 Transcription (DNA  RNA)
Ø Only one strand is
transcribed, with RNA
polymerase using
ribonucleotide
triphosphates (NTPs) to
build a strand in the 5’3’
direction
– Thus, the DNA is
transcribed (copied or
read) in the 3’  5’
direction
– The DNA strand that is
read is called the
template strand
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 Transcription (DNA  RNA)
Ø Upstream means toward the 5’ end of the RNA
strand, or toward the 3’ end of the template strand
(away from the direction of synthesis)
Ø Downstream means toward the 3’ end of the RNA
strand, or toward the 5’ end of the template strand

Upstream Downstream

The gene anatomy 49

 Transcription (DNA  RNA)
Ø Nucleotide triphosphates
are added to the growing
strand at the 3’ end
Ø Phosphodiester bonds are
made by DNA dependent
RNA polymerases
– Two phosphates are
lost from each
nucleotide triphosphate
Ø Note the antiparallel,
complementary strands

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Ø Transcription
has three stages
Initiation
Elongation
Termination

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 Initiation
Ø Requires a promoter – site where RNA polymerase
initially binds to DNA
– promoters are important because they are needed
to allow RNA synthesis to begin
– promoter sequence is upstream of where RNA
strand production actually begins
– promoters vary between genes; this is the main
means for controlling which genes are transcribed
at a given time
promoter Transcribed DNA sense strand
3’

3’
mRNA transcript
downstream
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Transcription (DNA  RNA)
Initiation

ØBacterial promoters
– about 40 nucleotides long
– positioned just before the point
where transcription begins
– recognized directly by RNA
polymerase

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 Initiation
ØEukaryotic promoters (for
genes that use RNA
polymerase II)
– Initially, transcription factors bind
to the promoter; these proteins
facilitate binding of RNA
polymerase to the site
– Transcription initiation complex
• Completed assembly of
transcription factors and RNA
polymerase at the promoter
region
– Allows initiation of transcription (the
actual production of an RNA strand
complementary to the DNA
template)
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 Initiation
Ø Regardless of promoter
specifics, initiation begins
when RNA polymerase is
associated with the DNA
– RNA polymerase opens
and unwinds the DNA
– RNA polymerase
begins building an RNA
strand in the 5’3’
direction,
complementary to the
template strand
– Only one RNA strand is
produced 55
 Elongation

Ø Transcription continues in a
linear fashion, with DNA
unwinding and opening
along the way
Ø The newly synthesized RNA
strand easily separates from
the DNA and the DNA
molecule “zips up” behind
RNA polymerase, reforming
the double helix

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 Termination
Ø Termination: the end of RNA transcription
– In prokaryotes,
transcription continues
until a terminator
sequence is transcribed
– usually a GC hairpin or
something similar
– That terminator
sequence (now in RNA)
causes RNA polymerase
to release the RNA
strand and release from
the DNA
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 Termination
– Termination in eukaryotes is more
complicated and differs for different RNA
polymerases
– Still always requires some specific
sequence to be transcribed
– For RNA pol II the specific sequence is
usually hundreds of bases before the
actual ending site

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 RNA processing

• Eukaryotic cells modify RNA

after transcription
• Addition of the 5 cap and poly-A tail
• Splicing

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Split Genes and RNA Splicing

Exon = Expressing sequences

Intron = Intervening sequences

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 Role of snRNPs and spliceosomes in mRNA splicing

Ø The process of removing introns is called RNA splicing

– The signals for splicing are short
sequences at the ends of introns
– Particles called snRNPs associate with
the mRNA in a complex called the
spliceosome
• snRNPs are made of small RNA
molecules and proteins
• The spliceosome catalyzes cutting
out and removing an intron and
joining together the exons
• RNAs in some of the snRNPs act as
ribozymes in the splicing process
• Note that the spliceosome is not
always required, but it usually is
needed 61
 Why do exons exist?
Ø Exons tend to code for specific domains within proteins
• A domain is a region within the
protein that has a specific function
• Exons with “junk DNA” intron
regions between them may be easy
to move around and rearrange to
make new proteins
• This leads to the notion that many
proteins consist of such functional
domains which can be readily
shuffled around during evolution to
produce new proteins with novel
functions
• Such exon shuffling does indeed
appear to have played a prominent
role in evolution in eukaryotes
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Translation:
a closer look

Translation is
the RNA-
directed
synthesis of a
polypeptide

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 Translation (RNA  protein)
Ø tRNAs bring amino acids to
the site of translation
• tRNAs are synthesized at
special tRNA genes
• tRNA molecules are strands
about 70-80 bases long that
form complicated, folded 3-
dimensional structures
• tRNAs have attachment sites
for amino acids
• Each tRNA has an anticodon
sequence region that will form
a proper complementary
basepairing with a codon on
an mRNA molecule
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 Translation (RNA  protein)
Ø tRNA is linked to the appropriate
amino acid by enzymes called
aminoacyl-tRNA synthetases
• The carboxyl group of each specific amino
acid is attached to either the 3' OH or 2'
OH group of a specific tRNA
• There is at least one specific aminoacyl-
tRNA synthetase for each of the 20 amino
acids used in proteins
• ATP is used as an energy source for the
reaction
• The resulting complex is an aminoacyl-
tRNA, also called a charged tRNA or
activated tRNA
• The amino acid added must be the proper
one for the anticodon on the tRNA
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 Translation
(RNA  protein)

Initiation
Elongation
Termination

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Translation Initiation

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Translation
Elongation

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 Translation Termination
Ø A stop codon signals the end for translation (UAA,
UGA, and UAG are universal stop codons)
Ø No tRNA matches the stop codon; instead, it a
termination factor (AKA release factor) binds there
Ø The termination factor causes everything to dissociate,
freeing the polypeptide, mRNA, last tRNA, and
ribosomal subunits all from each other (think of the
termination factor as a little molecular bomb)

69
OUTLINES

70
 Gene Expression
translation
DNAtranscription mRNA Protein

71
71
Genes can be expressed with different
efficiencies

Transcription and translation

are the means by which cells
re a d o u t , o r e x p re s s , t h e
genetic instructions in their
genes.

Ø Many identical RNA copies can be made from the same

gene, cells can synthesize a large amount of protein rapidly
when necessary.
Ø Each gene can also be transcribed and translated with a
different efficiency, allowing the cell to make vast quantities
of some proteins and tiny quantities of others.
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Differential Gene Expression
Signal

Ø Almost all the cells in an NUCLEUS

Chromatin

organism are genetically Chromatin modification

identical DNA
Gene available
for transcription

Ø Differences between cell Gene

Transcription

types result from RNA Exon

Primary transcript

differential gene
Intron
RNA processing

expression, the
Tail
Cap mRNA in nucleus

expression of different Transport to cytoplasm

genes by cells with the

CYTOPLASM
mRNA in cytoplasm

same genome Degradation

of mRNA
Translation

Ø Errors in gene expression Polypeptide

can lead to diseases Protein processing

including cancer Degradation

Active protein

Ø Gene expression is
of protein
Transport to cellular
destination

regulated at many stages Cellular function

73
 Signa
l
CYTOPLASM
NUCLEUS mRNA in cytoplasm
Chromatin

Translation
Chromatin Degradation
modification of mRNA

DNA
Gene available
for Polypeptide
Gene transcription
Transcription Protein processing

RNA Exon
Primary transcript
Intron Active
Degradation protein
RNA processing of protein
Tail Transport to cellular
destination
Cap mRNA in
nucleus
Transport to Cellular
cytoplasm function
CYTOPLAS
M
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Chromatin Structure and DNA Packing

7575
 Regulation of
Chromatin Histone
tails
Structure
Amino
acids
available
Ø Histone acetylation, DNA for chemical
double helix modification
acetyl groups are
attached to positively
charged lysines in (a) Histone tails protrude outward from a
histone tails nucleosome
Ø This process loosens
chromatin structure,
thereby promoting the
initiation of
transcription
Unacetylated histones Acetylated histones

(b) Acetylation of histone tails promotes loose

chromatin structure that permits transcription
76
 Histone Modifications
v The histone code hypothesis proposes that specific
combinations of modifications help determine
chromatin configuration and influence transcription

NH3+

-K9 Ac Me
Nucleosome P S10-
DNA
-K14 Ac

-K18 Ac

H2B H2A
-K27 Me
H4 H3 P S28-
DNA
H3
Octameric
histone core
77
 Epigenetic Inheritance

Ø Although the chromatin modifications just discussed

do not alter DNA sequence, they may be passed to
future generations of cells
Ø The inheritance of traits transmitted by mechanisms
not directly involving the nucleotide sequence is
called epigenetic inheritance

In biology, the term epigenetics refers to changes in

phenotype (appearance) or gene expression caused
by mechanisms other than changes in the underlying
DNA sequence, hence the name
epi- (Greek: over; above) -genetics.

78
 Organization of Eukaryotic Gene
Ø Associated with most eukaryotic genes are
control elements, segments of noncoding DNA
that help regulate transcription by binding
certain proteins
Poly-A signal
sequence
Enhancer Proximal
(distal control elements)
Termination
control elements region
Exon Intron Exon Intron Exon
DNA
Upstream Downstream
Promoter Transcription

Primary RNA Exon Intron Exon Intron Exon

Cleaved 3 end
transcript 5 of primary
RNA processing transcript

Intron RNA Poly-A

signal
Coding segment
mRNA 3
Start Stop
5 Cap 5 UTR codon codon 3 UTR Poly-A
tail
79
The Roles of Transcription Factors

• To initiate transcription, eukaryotic RNA

polymerase requires the assistance of
proteins called transcription factors
• General transcription factors are
essential for the transcription of all
protein-coding genes

80
 Activators Promoter
Gene
DNA
Enhancer Distal control TATA
element box
General
transcription
• Proximal control elements are factors
located close to the promoter DNA-bending
protein
• Distal control elements,
groups of which are called Group of
enhancers, may be far away mediator proteins
from a gene or even located in
an intron
RNA
• An activator is a protein that polymerase II
binds to an enhancer and
stimulates transcription of a
gene
• Bound activators cause
RNA
mediator proteins to interact polymerase II
with proteins at the promoter
Transcription
initiation complex RNA synthesis
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 Enhancer Promoter
Combinatorial
Albumin gene
Control of Gene Control
elements
Activation Crystallin gene

v A particular
combination of LIVER CELL LENS CELL
control elements NUCLEUS NUCLEUS

can activate Available

activators Available
transcription only activators

when the
appropriate
activator proteins Albumin gene
are present Albumin gene
not expressed
expressed

Crystallin gene
not expressed
Crystallin gene
expressed
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(a) Liver cell (b) Lens cell
1. Explain how Preimplantation Genomic
Dianosis (PGD) and Fetal Testing can be used
in genetic screening and counseling?
2. Explain why lethal dominant genes are much
rarer than lethal recessive genes
3. Describe replicating at the ends of eukaryotic
chromosomal DNA. How telomerase enzymes
lengthens telomeres?

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1. What is the difference between transcription
and translation. Describe the events of
initiation, elongation, and termination of
transcription and translation.
2. Describe the method of germline gene
therapy to prevent inherited mitochondrial
diseases passed from mother to child.

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1. What is epigenetic Inheritance? Explain how
histone acetylation affect chromatin structure
and the regulation of transcription.
2. Explain the role of promoters, enhancers,
activators, and repressors in transcription
control
3. Why is regulation of gene expression important?
How can, for example, a cell in the retina of
your eye make different proteins from a cell in
your liver when both cells have exactly the
same DNA?

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