Example Promoters Flashcards
(8 cards)
Name the 3 stages of transcriptional control.
Interferon-B promoter
- Constitutive repression
- Induction
- Post-induction repression
Name the activator proteins that recognise the INF-b enhancer.
INF-b
ATF2 c-Jun
IRFs (4 binding sites, 3 and 7 most important)
NFkB (p50 and RelA)
HMGA1
How is INF-b tightly regulated?
INF-b
NF-kB is sequestered in the cytoplasm by IkB
IRF3 remains in the cytoplasm until it is activated by phosphorylation
ATF2 c-Jun cannot activate transcription until it is phosphorylated
IRF7 is not consititutively expressed
Describe the two models of post-induction repression.
IFN-b
- Transcription factors bind the enhancer and lead to repressor:
NFAT5 binds to a site overlapping the IRF binding site, ATF3 binds and recruits HDACs, IRF2 replaces IRF3/7 (does not contain activation domain), Blimp-1 blocks activator binding and contains repressive epigenetic marks. - Removal of activator protein.
Phosphorylation of IRF3 tagets it for proteasomal degradation.
Describe consitiutive repression.
IFN-b
NRF binds to enhancer, overlapping where KFkB binds, YY1 binds and leads to heterchromatin formation, p50 homodimers bind and repress transcription.
How does corona virus block transcription of IFN-b?
IFN-b and Corona
nsp14 and nsp16 allow viral RNA to mimic host mRNA. Membrane protein (M) sequesters innate sensors and signalling molecules. Nucleocapsid protein (N) inhibits IRF3. nsp3 blocks phosphorylation of IRF3. nsp3, ORF3b and ORF6 block nuclear translocation of IRF3. nsp1 inhibits phosphorylation of STAT1 and ORF6 blocks nuclear translocation of STAT1.
How does corona virus disrupt epigenetic processes?
IFN-b and corona
ORF8 contains ARK seq found in H3. Mimicking of H3 leads to GCN5 degradation, thus gene repression.
How is long COVID related to epigenetics?
IFN-b and corona
Alters the balance of myelopoiesis and erythropoiesis.
