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Majority of regulation in bacterial takes place at what level
Transcriptional level (production of mRNA)
Expression pattern of house keeping gene
Constitutive (always expressed)
binding site for proteins that help regulate gene expression
where is it
downstream adjacent to the promoter
two types of regulatory proteins
where do they bind
repressor - bind to operator
activator- bind near the promoter
Bacteria favors which form of food? Glucose vs. Lactose
Glucose. Hence, when glucose is present Lac operon (for digesting lactose) is turned off.
3 protein products formed when lactose is present
what do they code for, their function
LacZ, A, Y (ZAY!!!)
- LacZ : B-galactosidase (breaks down lactose to form galactose and glucose
- LacA : Transacetylase (transferase- does not transfer, unknown function)
- LacY : Permease ( transport lactose)
Gene controlling component of the Lac operon
lacP, lacO, lacI--------OPI (operator, promoter, inhibitor)
what happens in Lac operon system when there is no lactose present?
Repressor(made from lacI) binds to lacO and the lac operon system and the lac Z, A, Y will not be transcribed
what happens when the lactose is present?
the isoform of lactose, allolactose will bind to the repressor sitting at lacO. this binding will make the repressor fall off of lacO and the lac operon gets turned on. now lacZ, A, Y can be transcribed to digest lactose.
Outline signaling pathway of lac operon when no glucose is present
no glucose--active adenylyl cyclase--atp converted to cAMP--binds to CRP(cAMP Receptor Protein) or CAP ( catabolite activator protein)--binds to lacP(promoter region of the lac operon system )--activate transcription for lac operon (for digesting lactose) if lactose is present.
outline the signaling pathway effecting lac operon system when glucose is present
glucose--no cAMP--inactive CRP--no transcription in the lac operon system
Describe the only condition which lac operon will be transcribed ( explain in terms of the lactose and glucose)
only when lactose is PRESENT AND glucose is ABSENT. This way the repressor will be unbound (lactose present -allowing the repressor to change confirmation and fall off of the lacO) and the promoter is bound (glucose present activating cAMP)
Drug that disrupts RNA polymerase
CBR703 series, rifamycin, rifampin
disrupt ribosome preventing translation
kenamycin, neomycin, tetracyclin
- 30s inhibitor ( tetracyclin, kenamycin, gentamicin, streptomycin)
- 50s inhibitor ( erythromycin, chloramphenical, clindamycin, fusidic acid)
disrupt DNA replication, transcription and DNA repair ( not translation)
A change in the gene expressiong and phenotype without changing the gene itself
Is it heritable?
active/ inactive chromatin
- active= euchromatin ("eu" means true)
what base does mathylation occur
cytosine--yields 5 methyl cytosine
where does trans-acting factors bind to?
binds to cis-regulatory elements
where are trans-acting factors and cis-regulatory elements located from the gene to be regulated ( interms of same/ diff chromosome)
trans-acting factor genes are usually on the diff chromosome than the target gene to be controled, whereas the cis-regulatory elements are on the same chromosome as the target gene.
de novo methylase
Dnmt3 (DNA methyl transferase 3)
protein that binds to methylated cytosine
MeCP2 (methyl-cytosine binding protein)
chromatin remodeling complex, recruited to the DNA by MeCP2
deacetylate lysine residue on the histone tail---gene inactivation
Sin3a & HDAC1/2 (histone deacetylase 1/2 complex)
maintain methylase for hemi-methylated DNA
matintain transcription repression during cell division
ICF (immunodeficiency centromeric instability facial anomalies syndrome) is due to the mutation in
Mutation in X linked gene (MeCP2) results in
Rett syndrome - more prevalent in girls
what happens to the imprinted allele
imprinting pattern depends on
it is inactivated and not expressed. depends on parental origin. Genomic imprinting has monoallelic expression pattern.
switching of globin gene is done by which DNA modification mechanism?
methylation ( at the promotor region coding for globin protein)
prader willi and angelman both involve deletion in which chromosome
prader willi syndrome is due to
snrpn deletion ( MATERNAL deletion at region 2)
Angelman Syndrome is due to
Deletion in UBE3A gene ( paternal deletion in region 1)
abnormal methylation is associated with
eg. methylation of tumor supressor genes, IGF( insulin like growth receptor) can be abnormally methylated
Drugs used to treat abnormal methylation, deacetylation
5 aza cytidine, sodium butyrate
repressor proteins reduce transcription through
- (activator and repressor compete to bind to the enhancer sequence)
when activator cannot bind to the enhancer sequence because the repressor protein is already bound
True or False- different genes have similar cis-regulatory seq.
spatial and temporal coordination of gene regulation by expressing transcription factors in specific cells, particular times during embryonic development and under certain environmental conditions
iron storage protein
what happens to ferritin/ transferrin receptor coding process during high and low iron level?
- high iron- increase ferritin translation, reduce transferrin receptor translation
- low iron- block ferritin translation, increase tansferrin receptor translation
Defect in ferritin and transferrin receptor regulation
hyperferritinemia (iron overload)
describe the effects of IRP binding to IRE in 5 UTR and 3UTR
- IRP binding to IRE at 5 UTR- controls ferritin translation
- the binding at 3UTR- controls transferrin receptor mRNA degradation
how does miRNA regulate expression
- repress mRNA translation
- (bind to 3'UTR and prevent interaction with 7mC cap)
miRNA in tumors
miRNA are overexpressed in tumors