Chapter 18

Regulation of Gene Expression 

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-cells can adjust the activity of enzymes already present-typical of anabolic pathways-allow a cell to adapt to short-term fluctuations in the supply of a substance it needs-Ex. if tryptophan accumulates in a cell, it shuts down the synthesis of more tryptophan by inhibiting enzyme activity
Feedback inhibition
-cells can adjust the production level of certain enzymes; regulate the expression of genes encoding the enzymes -many enzymes can be switched on or off by changes in the metabolic status of the cell
Cell's regulation of production level of enzymes/ Operon Model
-5 genes that code for the subunits of these enzymes are clustered together on bacterial chromosome -a single promoter serves 5 genes -transcription gives rise to one long mRNA molecule that codes for the 5 polypeptides making up the enzymes in the tryptophan pathway -one on/off switch can control the whole cluster of functionally related genes (coordinate control)
E.coli Transcription Unit
-all the enzymes for the metabolic pathway are synthesized at one time -segment of DNA -positioned within the promoter or between the promoter and the enzyme coding genes -controls access of RNA polymerase to the genes
Operator
-the operator, the promoter, and the genes they control -entire stretch of DNA required for enzyme production -trp operon in E. coli genome
Operon
-operon can be switched off by this -binds to the operator and blocks attachment of RNA polymerase to the promoter, preventing transcription of the genes -specific for the operator of a particular operon (have no effect on other operons)-allosteric protein-inactive and active shapes-only if tryptophan binds to trp repressor at an allosteric site does the repressor protein change to active form that can turn operon off
Repressor
-repressor is the product of this (called trpR in E. trp operon)-located some distance from the operon it controls and has its own promoter-expressed continuously, though at a low rate-a few trp repressors are always present in E. coli cells
Regulatory gene
-tryptophan is this in the trp operon-small molecule that cooperates with a repressor protein to switch operon off -as tryptophan accumulates, more tryp molecules associate with trp repressors, which bind to trp operator and shit down production of trpy pathway enzymes
Corepressor
-transcription is usually on but can be inhibited when specific molecule binds allosterically tp a regulatory protein
Repressible operon
-usually off but can be stimulated when a specific molecule interacts with a regulatory protein (lac operon)
Inducible operon
-specific small molecule that inactivates the repressor-lac operon is always active and needs this to turn it off
Inducer
-the allosteric regulatory protein interacts with this small, organic molecule, which accumulates when glucose is scarce -This is used in E. coli to to sense the glucose concentration and relay the info to the genome
Cyclic AMP (cAMP)
-the regulatory protein -is an activator, protein that binds to DNA and stimulates transcription of a gene-when cAMP binds to it, CAP assumes its active shape and can attach to a specific site at the upstream end of the lac promoter -attachment increases affinity of RNA polymerase for the promoter--this increases the rate of transcription and stimulates gene expression (positive regulation) -helps regulate other operons that encode enzymes used in catabolic pathways
Catabolite activator protein (CAP)
-under dual control: negative control by the lac repressor, positive control by CAP-state of repressor, with or without bound allolactose, determines whether or not transcription of the lac operon's genes occurs at all-state of CAP, with or without cAMP, controls rate of transcription if operon is repressor-free (on/off switch and volume control)
Lac operon: control
-human cell prob expresses 20% of its genes at a time-almost all cells of an organisms contain an identical genome (not immune cells)-unique cells expressed in each type -difference between cell types due to this expression of different genes by cells with the same genome-only 1.5% of genes code for protein; the rest for RNA or not transcribed
Differential gene expression