| Feedback Inhibition | - A cell can regulate the production of enzymes by feedback inhibition or by gene regulation
- In feedback inhibition, the end product of a metabolic pathway shuts down further synthesis of the product by inhibiting enzyme activity |
| Regulating Gene expression? Operon model? | - Cells can adjust the production level of certain enzymes by regulating expression of the genes encoding the enzymes
- The control of enzyme production is thus at the level of transcription
- One basic mechanism for this type of regulation of groups of genes is called the operon model |
| Operator | - A cluster of functionally related genes can be coordinately controlled by a single “on-off switch”
- The switch is a segment of DNA called an operator, positioned within the promoter or, sometimes, between the promoter and enzyme-coding genes |
| Operon | An operon is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control |
| Repressor? Regulatory gene? | - The operon can be switched off by a protein repressor
- The repressor prevents gene transcription by binding to the operator and blocking RNA polymerase
- The repressor is the product of a separate regulatory gene, located some distance from the operon itself
- The repressor can be in an active or inactive form, depending on the presence of other molecules |
| Corepressor | - A corepressor is a molecule that cooperates with a repressor protein to switch an operon off
- FOR EXAMPLE: E. coli can synthesize the amino acid tryptophan when it has insufficient tryptophan. By default, the trp operon is on and the genes for tryptophan synthesis are transcribed. When tryptophan is present, it binds to the trp repressor protein, which turns the operon off. The repressor is in the active state only in the presence of its corepressor tryptophan. Thus the trp operon is turned off (repressed) if tryptophan levels are high |
| Which operon is usually on? | A repressible operon is one that is usually on; binding of a repressor to the operator shuts off transcription
EXAMPLE OF REPRESSIBLE OPERON: The trp operon |
| Which operon is usually off? | An inducible operon is one that is usually off; a molecule called an inducer inactivates the repressor and turns on transcription
EXAMPLE OF INDUCIBLE OPERON: The lac operon, it contains genes that code for enzymes used in the hydrolysis and metabolism of lactose. The entire transcription unit is under the control of one main operator and promoter. A regulatory gene, lacI, located outside the operon encodes a repressor protein that can switch off the operon. By itself, the lac repressor is active and switches the lac operon off. A molecule called an inducer inactivates the repressor to turn the lac operon on. In the case of the lac operon, the inducer is allolactose, an isomer of lactose. Allolactose binds the repressor protein, altering its shape of the repressor so it can no longer bind to the operator sequence. |
| What type of pathways do inducible enzymes function in? | Inducible enzymes usually function in catabolic [break down] pathways; their synthesis is induced by a chemical signal |
| What type of pathways do repressible enzymes function in? | Repressible enzymes usually function in anabolic [build] pathways; their synthesis is repressed by high levels of the end product |
| Regulation of the trp and lac operons and negative control of genes | Regulation of both the trp and lac operons involves negative control of genes because operons are switched off by the active form of the repressor |
| Positive Gene Regulation? Activator? | - Some operons are also subject to positive control through a stimulatory protein, called an activator of transcription
- When glucose (a preferred food source of E. coli) is scarce, a specific activator attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription
- When glucose levels increase, the activator detaches from the lac operon, and transcription returns to a normal, low level
- The ability to catalyze compounds like lactose enables cells deprived of glucose to survive |
| Differential gene expression | - Almost all the cells in an organism contain an identical genome
- Differences between cell types result from differential gene expression, the expression of different genes by cells with the same genome
- Abnormalities in gene expression can lead to diseases including cancer
- Gene expression is regulated at many stages, but is often equated with transcription |
| DNA Chromatin Modifications | - Genes within areas of highly packed DNA chromatin are usually not expressed
- Attachment of certain compounds can open DNA chromatin, thereby promoting the initiation of transcription while the attachment of other compounds can condense chromatin and reduce transcription |
| Regulation of Transcription Initiation (just a little note) | Regions of DNA can be made either more or less accessible for transcription factors to bind |
| Epigenetic Inheritance | - Although the chromatin modifications just discussed do not alter DNA sequence, they may be passed to future generations of cells
- The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance
- Epigenetic variations might explain cases where one identical twin develops a genetically based disease, while the other does not |
| Activator? Enhancer? | - An activator is a protein that binds to an enhancer which stimulates transcription of a gene
- Activators have two domains, one that binds DNA and a second that activates transcription
- Bound activators facilitate a sequence of protein−protein interactions that result in enhanced transcription of a given gene |
| Post-Transcription Regulation | - Transcription alone does not constitute gene expression
- Regulatory mechanisms can operate at various stages after transcription
- Such mechanisms allow a cell to rapidly fine-tune gene expression in response to environmental changes |
| alternative RNA splicing | - In alternative RNA splicing, different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns
- Alternative RNA splicing can significantly expand the repertoire of a eukaryotic genome
- It is a proposed explanation for the surprisingly low number of genes in the human genome |
| Noncoding RNAs play multiple roles in controlling gene expression? ncRNAs? | - A small fraction of DNA codes for proteins, and a very small fraction of the non-protein-coding DNA consists of genes for RNA such as rRNA and tRNA
- In the past, genes that did not encode a protein product or known functional RNA were considered “junk DNA.” However, some genomic studies have cast doubt on this description
- Roughly 75% of the human genome is transcribed in at some point in any given cell
- At least some of the genome is transcribed into noncoding RNAs (ncRNAs)
- Researchers are uncovering more evidence of biological roles for these ncRNAs every day
- This represents a major shift in the thinking of biologists |
| Cell differentiation | - During embryonic development, a fertilized egg gives rise to many different cell types
- Gene expression orchestrates the developmental programs of animals
- The transformation from zygote to adult results from cell differentiation, the process by which cells become specialized in structure and function. Differential gene expression results from genes being regulated differently in each cell type. |
| Induction | - The other major source of developmental information is the environment around the cell, especially signals from nearby embryonic cells
- In the process called induction, signal molecules from embryonic cells cause changes in nearby target cells
- Thus, interactions between cells induce differentiation of specialized cell types |
| Gene regulation systems and Mutations and Cancer | - The gene regulation systems that go wrong during cancer are the very same systems involved in embryonic development
- Mutations that alter normal cell growth and division can lead to cancer |
| Oncogenes? proto-oncogenes? | - Oncogenes are mutations in genes (genes are called proto-oncogenes) that code for proteins that stimulate normal cell growth and division
- An oncogene arises from a change that either increases the amount of the proto-oncogene’s product or in the activity of the protein |
| The genetic changes that convert proto-oncogenes to oncogenes fall into four main categories | - Epigenetic changes
- Translocations
- Gene amplification
- Point mutations |
| Tumor-suppressor genes | - Tumor-suppressor genes normally inhibit cell division
- Mutations that decrease protein products of tumor-suppressor genes may contribute to cancer onset
- Tumor-suppressor proteins normally:
- repair damaged DNA
- control cell adhesion
- act in cell-signaling pathways that inhibit the cell cycle |
| Multiple mutations | Multiple mutations are generally needed for full-fledged cancer; thus the incidence increases
with age |
| Cancerous cells at the DNA level | At the DNA level, a cancerous cell is usually characterized by at least one active oncogene and the mutation of several tumor-suppressor genes |
| Inherited factors that can lead to cancer | - Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes
- Mutations in the BRCA1 or BRCA2 gene are found in at least half of inherited breast cancers, and tests using DNA sequencing can detect these mutations |
| The Role of Viruses in Cancer | - A number of tumor viruses can also cause cancer in humans and animals
- Viruses can interfere with normal gene regulation in several ways if they integrate into the DNA of
a cell
- Viruses are powerful biological agents |
| Frameshift vs base-substitution mutations | Frameshift mutation causes changes in the reading frame of a gene, resulting in the expression of incorrect proteins. Insertions and deletions are the main reasons for frameshift mutations. Base substitution mutation causes changes in the DNA sequence due to the exchange of one base from another. They also produce incorrect proteins at the end if the mutation is not silent. |
