Biochemistry - Gene Regulation Flashcards
Housekeeping genes
Eukaroytic genes codiing for proteins maintaining metabolic activity.
Example of housekeeping genes.
GAL1, GAL7 and GAL10 for galactosee metabolism to convert galactose to G1P.
Monocistronic
Only one gene is contained for protein, also called a cistron
Operon
Gene clusters transcribed together to give a single mRNA
What regulates GAL7/1/10?
Galactose
How does GAL80 repress galactose transcription?
Binds and inactivates the activator protein GAL4
GAL4
Activates transcription of the GAL genes
GAL3 mechanism in presence of galactose?
Binds galactoses with ATP and binds GAL80, restricting it to the cytoplasm.
What happens when galactose is not present?
GAL80 is free to roam as GAL3 cannot repress it, GAL80 binds and represses GAL4 to prevent GAL synthesis.
What are the two mechanisms of transcription activator protein?
Indirectly by interacting with transcriptional machinery components then recruiting it to the site or directly by inaitation transcription of a pre-assembled transcription complex
What are the two ways TAP interact with DNA?
helix-turn-helix motif and zinc fingers
TAP zinc finger mechanism..
Zinc has affinity for 17BP sequence either end of gene with CCG triplet codon it recognises.
How does helix-turn-helix motif faciltiate its functiion?
Infiltrate dsDNA grooves.
Where are enhancers found?
Intergenic regions or on introns within the gene.
Example of a TAP?
Mammary tumour virus activated by glucocorticoid steroid hormones.
Importance of enhancers?
Allow genes to be transcribed when certain proteins are present as well as alter amplification of syntheiss.
Polycomb Group Proteins
Epigenetic regulators of transcription important in stem-cell identiy and differentiation.
DNA looping
The binding of two sites of DNA.
Mechanism of DNA looping
TAP interacts with transcriptionak complex to recruit it tto gene, formation begins with TFIID(contans TBP), binding TATA box promoter region and DNA minor groove bending it 80 degrees, a TAP links TFIID to enhancer, which also brings TBP into contact with tata box allowing RNAPII recruitment
Why is DNA looping important?
Allws promoters to activate genes thousands of BP
Structure of RNAP II
Consists of 12 subnuits found in the POL2 holoenzyme
Chromatin-Remodelling Complexes
Multiprotein complexes that restructure chromatin to allow its transcription.
Most common CRC?
Cytosine methylation and CpG islands.
Methylation
Addition of a methyl group to 5’ carbon
What does CPG methylation do?
Repress transcription activity.
Example of methylation fucnctional importance…
Inactive X chromosome and in 60-70% somatic cell CCpG islands are methylaed
Genomic Imprinting
Expression of one copy of a gene and supression of another.
Wher edoes imprinting sex-specific silencing occur?
Prader-wili syndrome and Angelman syndrome
What do PWS and AS share in common?
Deletions of 15q11
What genes are deleted in 15q11?
SNRPN, necdin and UBE3A.
Where are SNRPN, necdin and UBE3A imprinted?
SNRPN and necdin in the egg and UBE3A in the sperm.
What happens to the 15q11 genes in germ line?
Males UBE3A imprinted on both homologs and necdin SNRPN in females
What happens if wildtype imrpinted female implanted with sperm of 15q11 deletion?
Embryo have no active copy of SNRPN nor NECDIN resulting in PW
Why might imprinting occur?
If a father supresses genes to conserve resources at expense of fetus, imeediate production will be maximuse.
Alternative Splicing
Where splice sites in pre-mRNA are selected in alteranting combination to produce variably spliced mRNA
What does Alternative Splicing allow for?
Varying quantites and different types from the same gene of an mRNA
Example of alternative splicing?
Insulin in skeletal muscle cells has exon 11 removed whilst liver retains it
Why is exon 11 removed frfom insulin in skeletal muscle cells?
Increases its affinity for insulin
How does mRNA stability regulate mRNA?
Altering stability affects outcome of protines.
Two type of mRNA stability?
Deadenylation dependent pathway
Deadenylation independent pathway
Deadenylation dependent pathway
Where poly-a tail is trimmed to about 25-60NT making it susceptible to cap removal