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Lecture 17

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Western University
Biology 2581B
Susanne Kohalmi

Genetics Lecture 17 Notes Is it possible to examine at the transcription of genes in a quantitative manner? (Can we put numbers on the amount of transcription?) If so, what could this tell us about transcriptional regulatory networks? Goal: mathematical model of 2 simple genetic regulatory networks Y = the target gene X = the transcriptional activator “Quantifying” Gene Regulation:  Imagine the box (Y) – within the box represents the level of mRNA present within a cell  There are 2 things that are going to affect the level of Y in the cell – the rate of production and the rate of degradation  There is a source and a sink – the source is just transcription, while the sink has to do with degradation  Any message has a certain half-life in the cell – nothing lasts forever  The double triangle thing represents the regulation of b and a, which control how much Y you have  Why are the units for the rate of degradation different from the units of production? o If the rate of degradation is 0.1/minute, it means that 10% of Y is being degraded per minute at that instant in time o If a = 0.1 nmoles/time, it means that 10% of Y is degraded every minute o If you catch the system at this instant in time, at that instant, you have 1000 nmoles in the cell – that means that the degradation rate is going to be 100 nmoles/minute o If you catch the system at the instant when you have 100 nmoles in the cell – means that the degradation rate is going to be 10 nmoles/minute o 10nmoles/minute for every 100 nmoles that are present in the cell  cancel out nmoles and it just comes out to 0.1/unit time  The rate of change of Y is determined by the production rate minus the degradation rate  Dy/dt = b-ay o Dy/dt = 0 at steady state  Y steady state/a = production rate/degradation rate  To quantify amount of message, you only need to know the production rate and the degradation rate The transcription of a gene can be simulated with the help of specialized computer programs…  It is possible to “create” a gene that transcribes with a given production and degradation rate within a computer program  In this way, the computer can handle the calculations and you can focus on the results The levels of Y mRNA will reach a steady state level within a cell based solely on production and degradation rates:  Tell the computer what the production rate (b) and degradation rate (a) is and what the level of Y is at the start of the system  For the second one, decrease production rate by ½, while the degradation rate is the same  Given enough time, each gene hits a steady state  Gene F hits a higher steady state that gene G, which has a higher steady state than gene H The initial levels of Y mRNA will not affect the final steady state levels of the message:  No matter where you start, given enough time, the system is ALWAYS going to go to steady state Describing Activation Mathematically:  Now you want to look at the actual activation part so add in the activator to our model of transcription  Have gene Y with the polymerase binding site  add in X binding site  Some signal Sx will convert S to the activator form S*  now we get even more transcription than before  X* = CRP bound to cAMP  X = CRP  Sx = cAMP  The rate of production (promoter activity) is a function of x* because the more X* we have, the more transcription we have (Y promoterctivity is proportional to X*) Describing Activation Mathematically – Hill Function for an Activator:  This function does a pretty good job of describing transcription 
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