EUKARYOTIC GENOMES, ORGANIZATION, REGULATION, AND EVOLUTION
What is CHROMATIN?
the complex of DNA and proteins that makes up a eukaryotic chromosome; when the cell is not dividing, chromatin exists as a mass of very long, thin fibers that are not visible with a light microscope.
Describe REGULATED GENE EXPRESSION in EUKARYOTES?
-regulation of genes expressed at any given time
-control of gene expression can occur at many different stages in the pathway that lies between transcription of a gene and activity of the protein.
-the most important and commonly used strategy for regulating gene expression acts at the LEVEL OF TRANSCRIPTION- which genes are copied by the RNA polymerase.
What are the stages during which REGULATION OF GENE EXPRESSION may occur?
-regulation of chromatin structure
-regulation of transcription
-regulation of RNA processing
-regulation of translation
-regulation of protein degradation
What are HISTONES?
a small protein with a high proportion of positively charged amino acids that binds to the negatively charged DNA and plays a key role in its chromatin structure.
What is HISTONE ACETYLATION?
-the attachment of acetyl groups to certain amino acids of histone proteins.
-when histones are acetylated, the positive charges are neutralized and histone tails no longer bind to neighboring nucleosomes.
-this unfolding allows the transcription proteins to have greater access to the DNA to initiate TRANSCRIPTION.
What are the two levels of DNA packing?
(1) heterochromatin (tightly compacted form)
(2) euchromatin (less compacted form)
What is HETEROCHROMATIN?
non-transcribed eukaryotic chromatin that is so highly compacted that it is visible with a light microscope during interphase.
What is EUCHROMATIN?
the more open, unraveled form of eukaryotic chromatin that is available for transcription.
How does dense packing of DNA in chromosomes prevent gene expression?
When the DNA is more compacted, the transcriptional machinery cannot access the DNA & therefore transcription is not active for the genes in that region.
Describe REGULATION OF TRANSCRIPTION in PROKARYOTES.
-regulation of transcription is needed for the cell to quickly adapt to the ever-changing outer environment.
-done by a cluster of functionally related genes that can be under coordinated control by a single on-off switch.
-the regulatory switch is a segment of DNA called the OPERATOR, usually positioned with the PROMOTER.
-an OPERON is the entire stretch of DNA that includes the operator, the promoter, and the genes they control.
What is an OPERATOR?
the segment of DNA that acts as a regulatory switch
What is the OPERON?
the entire stretch of DNA that includes the OPERATOR, PROMOTER, and the genes they control.
Describe how E. coli can metabolize lactose in the absence of glucose.
-requires galactoside permease which allows lactose to enter the cell.
-requires B-galactosidase to catalyze the hydrolysis of lactose to galactose and glucose.
-E. coli can then use glucose via glycolysis.
-converts galactose to glucose via glycolysis.
-when lactose is present, the repressor becomes inactivated and the lac operon is allowed to be transcribed.
What are the CONTROL ELEMENTS OF A GENE?
(1) core promoter (not a control element); leads to basal levels of transcription.
(2) PROXIMAL CONTROL ELEMENTS; located close to the core promoter; activators & repressors can bind.
(3) DISTAL CONTROL ELEMENTS; necessary for full activation/repression.
What is an ACTIVATOR?
protein that binds to an enhancer and stimulates transcription of a gene.
What is an ENHANCER?
-distal control elements
-DNA segment containing multiple control elements that may be located far way from the gene it regulates.
What are the steps of REGULATION OF TRANSCRIPTION in EUKARYOTES?
(1) ACTIVATORS BIND ENHANCERS
(2) DNA BENDS
(3) ACTIVATORS STABILIZE TRANSCRIPTION COMPLEX
What are some specific transcription factors?
(1) DNA BINDING DOMAIN (DBD): allows protein to bind to specific DNA sequences.
(2) ACTIVATION DOMAIN: allows protein to stabilize transcription initiation complex.
What is POST-TRANSCRIPTIONAL REGULATION?
alternate splicing generates different proteins from the same gene.
What is an INTRON?
a portion of a DNA or primary transcript sequence that DOES NOT CODE FOR PROTEIN.
Why are your liver and lens cells different?
because different genes are switched on and off in each type of cell.
What are ONCOGENES?
-a gene found in viruses or as part of the normal genome that is involved in triggered cancerous characteristics.
What are GAIN-OF-FUNCTION mutations?
-mutations that change the gene product such that it gains a new and abnormal function.
-these mutations usually have dominant phenotypes; only need one copy of the mutated gene to produce excessive cell division
-GROWTH-STIMULATING PATHWAY IS ENHANCED.
What are PROTO-ONCOGENES?
normal cellular genes that code for proteins that stimulate normal cell growth.
How can gene regulation cause cancer?
MUTATIONS that alter genes that normally regulate cell growth and division during the cell cycle include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways.
Interference with what CONTROL SYSTEMS can cancer result from?
-CELL CYCLE-STIMULATING PATHWAY.
-CELL CYCLE-INHIBITING PATHWAY.
-EFFECTS OF MUTATIONS.
How might a proto-oncgogene (a gene that has essential function in normal cells) become an oncogene (a cancer-causing gene)?
an oncogene arises from a genetic change that leads to an increase either in the amount of the proto-oncogenes protein product or in the instrinsic activity of each protein molecule.
What are the 3 main categories of genetic changes that convert proto-oncogenes into oncogenes?
(1) movement of DNA within the genome.
(2) amplification of a proto-oncogene.
(3) point mutations in a control element or in the proto-oncogene itself.
Where does a point mutation occur to cause cancer?
-in the promoter or enhancer that controls a proto-oncogene, causing an increase in its expression
-in the coding sequence, changing the gene's product to a protein that is more active or more resistant to degradation that the normal protein.
What is the RAS GENE?
-G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases.
-if Ras has been activated, cells will begin to divide rapidly.