bonus #1 is due 10/02 more regulating gene expression
TRANSCRIPT
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Bonus #1 is due 10/02
More Regulating Gene Expression
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Combinations of 3 nucleotides code for each 1 amino acid in a protein.
We looked at the mechanisms of gene expression, now we will look at its regulation.
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Why change gene expression?
•Different cells need different components•Responding to the environment•Replacement of damaged/worn-out parts
Fig 15.1
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Two points to keep in mind:
1. Cellular components are constantly turned-over.
2. Gene expression takes time:Typically more than an
hour from DNA to protein. Most rapidly 15 minutes.
Fig 15.1
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•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
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In bacteria, transcription and translation occur simultaneously. So most regulation of gene expression happens at transcription.
Fig 13.22
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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
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Fig 14.3
Operon: several genes whose expression is controlled by the same promoter
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Fig 14.3E. coli lactose metabolism
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Fig 14.4 In the absence of lactose, the lac operon is repressed.
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Fig 14.4 Lactose binds to the repressor, making it inactive, so that transcription can occur.
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Fig 14.5
Repression or induction of the lac operon
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Fig 14.3 There is more to lac gene expression than repression
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Fig 14.8 Glucose is a better energy source than lactose
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Fig 14.8 Low glucose leads to high cAMP
cAMP binds to CAP which increases lac operon transcription
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Fig 14.8High glucose leads to low cAMP
low cAMP, CAP inactive, low lac operon transcription
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Fig 14.3
The lac operon: one example of regulating gene expression in bacteria
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Overview of transcriptional regulation
Fig 14.1 and 15.1
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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
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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
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Tightly packaged DNA is unavailable. DNA packaging changes as the need for different genes changes.
Fig 10.21
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Different levels of DNA packaging Fig 10.21
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Histones can be post-translationally modified, which affects their abililty to bind DNA.
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Acetylation (-COCH3): post-translational modifications of the histones loosen DNA binding
Fig 12.15
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Acetylation of histones (-COCH3) causes a loosening of the DNA/histone bond…unpackaging the DNA.
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Fig 15.13DNA methylation
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Fig 15.14
DNA methylation often inhibits transcription
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Fig 15.15Epigenetics:the inheritance of DNA modifications, including methylaton
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Four-stranded DNA: cancer, gene regulation and drug developmentby Julian Leon HuppertPhilosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering SciencesTriennial Issue of 'Chemistry and Engineering’DOI: 10.1098/rsta.2007.0011Published: September 13, 2007
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4 strand DNA Fig 1
Four-stranded DNA forms between sequences of guanines…G-quadruplexes
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4 strand DNA Fig 1
Four-stranded DNA forms between sequences of guanines…G-quadruplexes
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4 strand DNA Fig 2
The G-quadruplexes can form from 4, 2, or 1 DNA strand.
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Fig 10.11
During DNA replication, the ends of the DNA are not completely copied.
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Telomeres are non-gene DNA at the ends of DNA strands.
Telomeres are shortened during DNA replication.
Fig 10.11
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Fig 11.25
Telomeres can be lengthened by telomerase.
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The telomeric cap structure is one place where G-quadruplexes can be found
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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.
Fig 10.11
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Drugs that can block the action of telomerase, by binding the G-quadruplexes, are being
investigated to treat cancer.
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Fig 12.13
Eukaryotic promoters often contain G-rich areas
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4 strand DNA Fig 5
G-quadruplex in promoters
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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
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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
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G-quadruplex ligands
G-quadruplex
BRACO-19
TMPyP4
telomestatin
4 strandDNAFig 6
Down regulates telomerase and some oncogene transcription
Specifically binds to telomeres, naturally occurring in Streptomyces anulatus
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4 strand DNA Fig 7
Model of specific G-quadruplex ligand binding to G-quadruplex and a specific DNA sequence
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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
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Bonus #1 is due 10/02
More Regulating Gene Expression