Bonus #1 is due 10/02 More Regulating Gene Expression

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.

Why change gene expression? Different cells need different components Responding to the environment Replacement of damaged/worn-out parts Fig 15.1

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

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

Fig 14.8 High glucose leads to low cAMP low cAMP, CAP inactive, low lac operon transcription

Fig 14.3 The lac operon: one example of regulating gene expression in bacteria

Overview of transcriptional regulation Fig 14.1 and 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 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational Fig 15.1

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 post- translationally modified, which affects their abililty to bind DNA.

Acetylation (-COCH 3 ) : post-translational modifications of the histones loosen DNA binding Fig 12.15

Acetylation of histones (-COCH 3 ) causes a loosening of the DNA/histone bond…unpackaging the DNA.

Fig DNA methylation

Fig DNA methylation often inhibits transcription

Fig Epigenetics: the inheritance of DNA modifications, including methylaton

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: /rsta Published: September 13, 2007

4 strand DNA Fig 1 Four-stranded DNA forms between sequences of guanines…G-quadruplexes

4 strand DNA Fig 1 Four-stranded DNA forms between sequences of guanines…G-quadruplexes

4 strand DNA Fig 2 The G- quadruplexes can form from 4, 2, or 1 DNA strand.

Fig During DNA replication, the ends of the DNA are not completely copied.

Telomeres are non-gene DNA at the ends of DNA strands. Telomeres are shortened during DNA replication. Fig 10.11

Fig Telomeres can be lengthened by telomerase.

The telomeric cap structure is one place where G-quadruplexes can be found

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

Drugs that can block the action of telomerase, by binding the G-quadruplexes, are being investigated to treat cancer.

Fig Eukaryotic promoters often contain G-rich areas

4 strand DNA Fig 5 G-quadruplex in promoters

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: /rsta Published: September 13, 2007

Oncogenes, the genes involved in cancer, are especially rich in potentially regulatory quadruplexes—69% of them have such motifs

G-quadruplex ligands G-quadruplex BRACO-19 TMPyP4 telomestatin 4 strand DNA Fig 6 Down regulates telomerase and some oncogene transcription Specifically binds to telomeres, naturally occurring in Streptomyces anulatus

4 strand DNA Fig 7 Model of specific G-quadruplex ligand binding to G-quadruplex and a specific DNA sequence

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

Bonus #1 is due 10/02 More Regulating Gene Expression