8 Regulation of gene expression Flashcards
how is genetic regulation and protein synthesis linked?
not all genes are transcribed at all times, only those that are needed are done at a per needed basis
constitutively transcribed genes are AKA housekeeping genes
how is genes expression protein synthesis always linked in prokaryotes
translation of mRNA begins before transcription is complete
what is translated is controlled by what mRNA is made
what is an operon?
set of polycistronic genes and their promotor that all encodes for different proteins that are used in a related pathway
how is the positive and negative controls for transcription done in prokaryotes?
positive control makes it so a protein is needed for transcription to initiate
negative control is through requiring a protein to inhibit the transcription process
what is the model operon that is used for most examples?
lac operon in which allows a bacteria to process lactose
give an example of repression and inducers with a lac operon
Lac operon is constitutively repressed. allolactose is an inducer that binds away the repressor.
lac operon also needs coactivation to be transcripted which is a cAMP-CRP(cat rec protein) to begin transcription which is why when glucose and lactose is present, it will prefer glucose thus lowering cAMP
what non specific factor will activate RNA polymerase in prokaryotes to bind to several promotors?
sigma factor
explain the attenuation of transcription
hairpin structural arrangements will determine if transcription occurs by attenuation
ie. trp operon w/ 4 domains and trp coded sequence initially
trp low –> ribosome stalls at trp sequence –> 2+3 binds allowing transcription to occur
trp high –> trp sequence does not stall ribo –> 3+4 binds which creates termination signal
what is a macrostructural feature of eukaryotes that can control transcription?
chromatin arrangement itself can regulate transcription
what are the 4 main differences of transcription between euks and proks
euks have no operons
euks separate transcription and translation in two diff compartments
euks have genes for proteins of same pathway on different chromosomes
DNA in euks are in nucleosomes
name the seven control steps in order for DNA regulation in euks
- chromosome/gene rearrangement
- transcription factors
- RNA editing during transcript processing
- RNA xport
- ribo activation
- mRNA stability
- protein stability
explain chromatin remodeling via histones
histones can be acetylated which will decrease the positive charges thus allowing unwinding of the negative DNA and allowing xcription.
reverse is true with histone deacetylation
explain DNA methylation
cytosine can be methylated
G-C rich sequences ie. CpG isalnds are the ones that are most heavily methylated
methylation can activate or repress
usually on promotor sequences
describe two related inherited disorders resulting from methylation
prader willi and angelmans syndromes originate from methylation of alternate sides but mutations lead to the side that covers for the methylated sequence is deleted. originates on chromosome 15
describe the four ways genomes in cells can be regulated at the DNA/chromosome level
gene rearrangement
amplification/deletion
chrom translocation
triplet repeats
explain and give an ie of gene rearrangement
segments of one DNA moving to another
ie. VDJ recombination then splicing similar to mRNA but then is retranscribed into mRNA, useful for b and t cell receptor genes
explain gene amplification and its results
NOT normal
some sequences replicated at a high rate abnormally
forms excised double minutes that can insert in random places and cause amplification of the sequence in protein form
explain gene deletions and translocations
deletions via errs of repl, division and damage
ie. loss of tumor suppressor -> cancer
translocations are when gene are abnormally relocated elsewhere thus affected by a diff promotor or gene
ie. 9:22 trans BCR+Abl 22- -> philadelphia chromosome -> CML
8: 14 trans -> burkitts lymphoma
Give two demonstrations of triplet repeats expansion syndromes
fragile X where CGG triplet is expanded on the 5’ end of the FMR-1 gene
60-230 is carrier any more are affected
Huntingtons have a CAG expansion where any more than 35 triplets will cause disease
means that triplet expansions can be additive over generations
Explain how external elements can affect transcription ie. steroid response
steroids like cortisol can bind with Hormone sensitive proteins found in cytosol which will then dimerize and xport to nucleus which will then bind with coactivator RNA polymerase complex and bind to NLS and activate transcription
How does androgen insensitivity occur?
defect steroid receptors in cells will cause failure of transcription and downstream effects thus cause ambiguous genitalia, but there may be high amounts of androgens present in the blood
How are the effects of thyroid hormone produced by target cells in the body?
TH receptors are bound to a RXR complex which w/o T3 it will bind to a corepressor with HDAC so as to halt transcription
w/T3 TH rec and RXR will bind to coactivator with HAC and thus initiate transcription of the proteins that mediates the downstream effects of T3
What are the four types of DNA binding domains?
zinc fingers, leucine zippers, helix turn helix, helix loop helix
all bind to the major groove of DNA via alpha helix
Name a specific receptor that uses a zinc finger type binding domain
estrogen receptors has a Zn complexes with four cystein residues in a protein that will form an alpha helix that will bind over with a NRS that recognizes the specific major groove of the DNA