chapter 18

Bio1151 Chapter 18 9

Regulation of protein production is an important aspect of the dogma.
- Protein activity can be regulated by
- feedback inhibition when the product of the metabolic pathway inhibits activity of the first enzyme in the pathway. Review:
- gene regulation when the genes coding for the enzyme are not transcribed (expressed).
The E. coli trp operon is a system that is turned unless repressed by the .
- An operon is a group of functionally related genes under the control by a single on-off "switch" called an operator which is usually located within the promoter. The E. coli trp operon contains 5 genes in the pathway for tryptophan (an amino acid) synthesis. A separate regulatory gene codes for a repressor that is normally inactive.
- operon on
- operon off
  Review:
- Tryptophan absent, repressor inactive, operon on. In the repressible trp operon, 5 genes encoding the enzymes to synthesize tryptophan are regulated by a promoter and an operator.
  When tryptophan is absent, the repressor (with its own promoter) is inactive and the operon is on. RNA polymerase attaches to the DNA at the promoter and transcribes the operon's genes.
- Tryptophan present, repressor active, operon off. The presence of tryptophan (a co-repressor) activates the repressor which binds to the operator to turn the operon off by inhibiting the transcription of these genes by RNA polymerase.
The E. coli lac operon is an system that is turned unless induced by the .
- E. coli uses 3 enzymes to take up and metabolize the sugar lactose.
  The genes for these 3 enzymes are clustered in the lac operon.
- operon off
- operon on
  Review:
- Lactose absent, repressor active, operon off. In the absence of lactose, an active repressor switches off the operon by binding to the operator.
- Lactose present, repressor inactive, operon on. Allolactose, an isomer of lactose, serves as an inducer and turns on the operon by inactivating the repressor. Transcription and translation of enzymes for lactose digestion proceeds.
Eukaryotic gene expression can be at many stages, from the nucleus to the cytoplasm.
- Eukaryotic gene regulation: nucleus.
- Chromatin modification: acetylation of histone "tails".
- Transcription control: activators can stimulate transcription.
- RNA processing: alternative RNA splicing.
- Chromatin modification.
  Enzymes can add negative acetyl groups (-COCH[3]) to histone tails.
  Histone acetylation loosens chromatin structure, making the DNA accessible to transcription.
  Such chromatin modifications may be passed to future generations of cells in a process called epigenetic inheritance.
- Activator proteins bind to an enhancer region in the DNA.
  A DNA-bending protein brings the bound activators closer to the promoter.
  The activators bind to transcription factors and mediator proteins, forming a transcription initiation complex.
  The complex promotes the binding of RNA polymerase to the promoter, enhancing gene expression.
  Review;
- RNA processing.
  The primary transcripts of some genes can be spliced in many ways, generating different mRNA molecules.
  In this example one mRNA molecule ends up with the green exon and the other with the purple exon.
  With alternative splicing, an organism can produce more than one type of polypeptide from a single gene.
  Review:
- Eukaryotic gene regulation: cytoplasm.
- mRNA degradation: degradation of an mRNA in the cytoplasm limits its lifespan. Review 1:
- Protein processing: many proteins are activated by signal molecules in transduction pathways.
- Protein degradation: proteasomes degrade proteins at the end of their useful lifespan. Review 2:
  Summary exercise:
- mRNA degradation.
- Single-stranded microRNAs (miRNAs) can form double-stranded regions by hydrogen bonding.
- The single-stranded loops are cut by the Dicer, and one strand is degraded.
  The remaining miRNA strand forms a complex with proteins, and can degrade complementary mRNA or block its translation.
- Protein degradation.
  Unneeded proteins can be tagged with the protein ubiquitin.
  The tagged protein is then chopped up by protein complexes called proteasomes.
Multicellular organisms develop from a single-celled to cells of many different types through cell , cell , and morphogenesis.
- Differences between cells is mainly due to differential gene expression, even though different cells share genomic equivalence (have the same genes).
- Morphogenesis encompasses the processes that give shape to the organism and its parts. It takes just one week for cell division, differentiation, and morphogenesis to transform a fertilized frog egg into a hatching tadpole.
- Differential distribution of determinants in the egg can lead to subsequent of embryonic cells.
  - Cytoplasmic determinants.
    The distribution of cytoplasmic determinants, such as RNA, proteins, and organelles, may be uneven in the unfertilized egg
    Such uneven beginnings may affect expression of genes after the first cell division.
  - Induction by nearby cells.
    The cells at the bottom of this early embryo release signal molecules that induce nearby cells to change their gene expression (transcription).
  - Cytoplasmic determinants establish the axes of the body in Drosophila.
    Asymmetrically distribution of these molecules in the unfertilized egg eventually lead to differentiation of specialized segments of the adult.
    One important cytoplasmic determinant is mRNA produced by the bicoid gene.
    Review;
  - Gradients of bicoid mRNA and bicoid protein in egg and early embryo leads to normal development of body segments.
  - A mutation in the mother's bicoid gene leads to tail structures at both ends in the Drosophila mutant embryo.
- Expression of genes for tissue-specific proteins result in cell , and leads to observable .
- Cell determination.
  MyoD is a "master regulatory gene" whose expression commits the cell to becoming skeletal muscle.
  If a myoblast cell produces the MyoD protein (a transcription factor), it binds to enhancers of many target genes.
  The cell is now determined to be a skeletal muscle cell.
Genetic mutations that affect cell cycle control can lead to .
- Abnormal cell division that leads to cancer can be caused by
- Increased expression of a proto-oncogene can cause over-stimulation of the cell cycle.
- Decreased expression of a tumor-suppressor gene can cause inability to inhibit the cell cycle.
- Proto-oncogenes are normal genes involved in cell growth and division. Mutations to a proto-oncogene can lead it to become a cancer-causing oncogene by producing growth-stimulating proteins that are in excess levels or that are hyperactive or degradation - resistant.
- The p53 tumor suppressor gene encodes a transcription factor that regulates transcription of more than 50 different genes involved in the cell cycle.
  p53 and Adenovirus
mutations are generally needed for full-fledged cancer.
- Development of colorectal cancer (affecting the colon and/or rectum) involves multiple stages.
- stage 1
- stage 2
- stage 3
- Mutations affecting tumor-suppressor genes may lead to benign (non-invasive) growth in the colon lining called a polyp.
- Mutations in other tumor-suppressor genes and development of oncogenes can cause enlargement of the benign growth into an adenoma.
- Continued accumulation of mutations can culminate in the development of full-fledged cancer, invading other tissues.
  This malignant tumor is called a carcinoma.