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Regulation of Gene Expression
Medical School Biochemistry
23
Biochemistry
Graduate
08/28/2011

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Term
What is an operon?
Definition
A group of genes regulated together by a promoter
Term
What is a Shine-Dalgarno sequence?
Definition
A functional analog to the 5' cap in eukaryotic mRNA synthesis. A vital piece necessary to commence translation
Term
How does the lac operon work?
Definition
The lac operon works with a two tiered logic switch.

The first is a CRP binding site, unless this site is bound by CRP then the lac operon will not work (only bound by CRP when Glucose levels are low in the ambient environment.

The second level a lac repressor. The lac repressor remains on the lac operator unless lactose is present in the ambient environment.

To initiate transcription of mRNA that codes for lactose metabolism both the CRP binding site has to be bound (low glucose) and the lac operon represser released (lactose must be present in the ambient environment). This allows for preferential metabolism of glucose
Term
Hoe does the trp operon work?
Definition
Trp has only a repressor that will be attach to the operon if sufficiently high levels of Tryptophan are in the cell
Term
In Eukaryotes, how are genes put in the off position?
Definition
Methylation, specifically of CpG islands
Term
What is epigenetic inheritance?
Definition
Preservation of the methylation patterns after cellular replication
Term
What are two common example of gene methylation in humans?
Definition
Barr Bodies and imprinting.

Barr Bodies are inactivated X chromosomes in females

Gene imprinting is the use of methylation to determine expression of phenotype
Term
What is the clinical relevance of microsatellite instability?
Definition
Microsatellite instability can be of prognostic and diagnostic value in detecting cancers.

Many cancers (such as Lynch's Syndrome) arise from errors in strand-directed mismatch repair, these errors will also result in more Microsatellities
Term
How does RNA transcription and subsequent translation occur in light of the presence of methylation and histones?
Definition
Proteins exist that help unwind this DNA, these proteins were covered in earlier lectures but know that RNA transcription would not be able to occur with out Chromatin remodelling complexes and histone chaperones
Term
What are the three main domains of gene specific transcription factors?
Definition
1. DNA binding domain
2. Dimerization Domain
3. Activation Domain
Term
What are DNA binding Domains?
Definition
These are the transcription factors that are present close to the promoter of interest, assures that the desired mRNA is being coded
Term
What are Dimerization Domains?
Definition
Interaction between proteins (like or unlike) that promote transcription
Term
What is an activation domain?
Definition
Protein that interacts with RNA polymerase
Term
What are two famous helix-turn-helix transcription factors? How do helix-turn-helix factors work?
Definition
Hox and Trp. Helix-turn-helix factors work by binding on the major groove of DNA
Term
What do Hox genes code for?
Definition
These genes are turned on during development to allow for cranial to caudal differentiation. Turned on by the Hox helix-turn-helix transcription factor
Term
What are Zinc-finger transcription factors?
Definition
a transcription factor bound together by Zinc that also works by binding to the major groove of DNA
Term
How do zinc-finger transcription factors work?
Definition
All zinc-fingers have a common set-up. Zinc fingers have a DNA binding region, a transcription activating domain, and a ligand-binding domain.

Once the zinc-finger comes in contact with its ligand it breaks free from its inhibitory proteins and attaches to a specific point in the DNA. From there the zinc-finger transcription factor interacts with other proteins to increase transcription of the given gene
Term
What are some common zinc-finger ligands?
Definition
cortisol
estrogen
progesterone
vitamin D
thyroid hormone
retinoic acid
Term
How do gluco-corticoids help with asthma attacks?
Definition
They are the ligands for a zinc-finger transcription factor which codes for proteins that knock down inflammation.
Term
How do leucine zipper transcription factors work?
Definition
leucine zippers interact with DNA through charge mechanics (basic leucine with acidic DNA). Hydrophobic leucine residues face each other and that gives rise to the characteristic zipper appearance
Term
How do helix-loop-helix transcription factors work and how are they differentiated from helix-turn-helix transcription factors?
Definition
Helix-loop-helix transcription factors work with acid-base chemistry like leucine zippers. They are different from Helix-turn-Helix in that the loop is much shorter then the turn in Helix-turn-Helix
Term
What are the two ways the miRNA regulate mRNA?
Definition
1. by causing a double strand and then slicing the mRNA, it is afterwords quickly metabolized by RNAse

2. By binding to the mRNA and lowering translation rates
Term
What is a RISC?
Definition
RNA induced silencing complex. This is the complex the miRNA binds to
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