Transcript 9/30 - Utexas

More Regulating Gene Expression
Bonus #1 is due 10/02
We looked at the
mechanisms of
gene expression,
now we will look
at its regulation.
Combinations of
3 nucleotides
code for each 1
amino acid in a
protein.
Fig 15.1
Why change gene
expression?
•Different cells need
different components
•Responding to the
environment
•Replacement of
damaged/worn-out parts
Two points to keep in
mind:
1. Cellular components
are constantly turnedover.
2. Gene expression takes
time:
Typically more than an
hour from DNA to
protein. Most
rapidly 15 minutes.
Fig 15.1
•Gene expression can be
controlled at many
points between DNA and
making the final
proteins.
•Changes in the various
steps of gene expression
control when and how
much of a product are
produced.
Fig 15.1
In bacteria, transcription and translation occur
simultaneously. So most regulation of gene
expression happens at transcription.
Fig 13.22
Transcription initiation in prokaryotes:
sigma factor binds to the -35 and -10 regions and then
the RNA polymerase subunits bind and begin
transcription
Fig 12.7
Fig 14.3
Operon: several genes
whose expression is
controlled by the same
promoter
Fig 14.3
E. coli lactose metabolism
Fig 14.4
In the absence of lactose, the lac
operon is repressed.
Fig 14.4
Lactose binds to the repressor, making it
inactive, so that transcription can occur.
Fig 14.5
Repression or induction of the lac operon
Fig 14.3
There is more to lac gene expression
than repression
Fig 14.8
Glucose is a better energy source
than lactose
Fig 14.8
Low glucose leads to high cAMP
cAMP binds to CAP which increases lac
operon transcription
High glucose leads to low cAMP
low cAMP,
CAP
inactive, low
lac operon
transcription
Fig 14.8
Fig 14.3
The lac operon: one
example of regulating
gene expression in
bacteria
Overview of transcriptional regulation
Fig 14.1 and 15.1
Gene Expression is controlled
at all of these steps:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 15.1
Fig 16.1
Gene Expression is controlled
at all of these steps:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 15.1
Fig 16.1
Tightly packaged DNA is unavailable. DNA
packaging changes as the need for different
genes changes.
Fig 10.21
Different levels of DNA packaging
Fig 10.21
Histones can be posttranslationally
modified, which
affects their abililty
to bind DNA.
Fig 12.15
Acetylation (-COCH3):
post-translational
modifications of the
histones loosen DNA
binding
Acetylation of histones
(-COCH3) causes a
loosening of the
DNA/histone
bond…unpackaging the
DNA.
Fig 15.13
DNA methylation
DNA methylation often inhibits transcription
Fig 15.14
Epigenetics:
the inheritance of
DNA modifications,
including
methylaton
Fig 15.15
Four-stranded DNA: cancer, gene regulation
and drug development
by Julian Leon Huppert
Philosophical Transactions of the Royal Society A: Mathematical,
Physical and Engineering Sciences
Triennial Issue of 'Chemistry and Engineering’
DOI: 10.1098/rsta.2007.0011
Published: September 13, 2007
Four-stranded DNA forms between sequences
of guanines…G-quadruplexes
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 1
Four-stranded DNA forms between sequences
of guanines…G-quadruplexes
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 1
The Gquadruplexes
can form from
4, 2, or 1 DNA
strand.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 2
Fig 10.11
During DNA replication, the
ends of the DNA are not
completely copied.
Fig 10.11
Telomeres are non-gene DNA at the
ends of DNA strands.
Telomeres are shortened during DNA
replication.
Fig 11.25
Telomeres can be
lengthened by
telomerase.
The telomeric cap structure is one place where
G-quadruplexes can be found
Fig 10.11
Telomeres are non-gene DNA at the
ends of DNA strands.
Short telomeres will cause cells to stop
replicating or cell death.
The critical size is unknown.
Drugs that can block the action of telomerase,
by binding the G-quadruplexes, are being
investigated to treat cancer.
Fig 12.13
Eukaryotic promoters often contain G-rich
areas
G-quadruplex in promoters
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 5
If the promoter is defined as 1 kbase upstream of the
transcription start site:
•Quadruplex motifs are significantly overrepresented
relative to the rest of the genome, by almost an order of
magnitude.
•almost half of all known genes have a putative
quadruplex-forming motif
•By comparison, the TATA box motif—probably the
best-known regulatory motif and a staple of
undergraduate textbooks—is found in only
approximately 10% of genes.
Four-stranded DNA: cancer, gene regulation and drug development by Julian Leon Huppert in Philosophical Transactions of the Royal
Society A: Mathematical, Physical and Engineering Sciences Triennial Issue of 'Chemistry and Engineering’ DOI: 10.1098/rsta.2007.0011
Published: September 13, 2007
Oncogenes, the genes involved in cancer, are
especially rich in potentially regulatory
quadruplexes—69% of them have such motifs
Four-stranded DNA: cancer, gene regulation and drug development by Julian Leon Huppert in Philosophical Transactions of the Royal
Society A: Mathematical, Physical and Engineering Sciences Triennial Issue of 'Chemistry and Engineering’ DOI: 10.1098/rsta.2007.0011
Published: September 13, 2007
G-quadruplex ligands
TMPyP4
BRACO-19
Down regulates telomerase and
some oncogene transcription
G-quadruplex
telomestatin
Specifically binds to telomeres, naturally
occurring in Streptomyces anulatus
4 strand
DNA
Fig 6
Model of specific G-quadruplex ligand binding
to G-quadruplex and a specific DNA sequence
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 7
Gene Expression is
controlled at all of these
steps:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 15.1
Fig 16.1
More Regulating Gene Expression
Bonus #1 is due 10/02