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Lecture 3

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Darrel Desveaux

Two Proteins That Repress Each Other's Synthesis Determine Heritable State of Bacteriophage Lambda  Irreversible change in DNA is a mechanism of cell differentiation in lymphocyte differentiation. Reversible DNA changes, (Salmonella, yeasts) responsible for some inherited changes in gene expression, not widely  used  Bacterial virus lambda, a switch causes the virus to flip flop between two stable self maintaining states. --> prototype for similar but more complex switch in higher eukaryotes  Lambda can remain silent in ecoli, multiply with the host or kill the host right away (depend on environment) or kill host right away. Protein mediate the switch (50 genes)  Virus that want to integrate, must produce integrate protein, insert lambda DNA into bacterial chromosome, must repress the production of viral proteins for multiplication  Lambda repressor protein, and Cro protein repress each other's synthesis --> give two stable states 1. State 1, prophage state  Lambda repressor occupies the operator, block the synthesis of Cro, activate its own synthesis  DNA of integrated bacteriophage is not transcribed 2. State 2, the lytic state  Cro protein occupies different site in operator, block the synthesis of repressor allow its own synthesis  DNA is extensively transcribed, replicated, packaged into new bacteriophage and release by host cell lysis Stage one if bacteria growing well, multiply with host.   Host is damaged, stage 2 to make quick exit --> response to DNA damage, inactivates repressor  Positive feedback loop maintain prophage state Simple Gene Regulatory Circuits Can Be Used to Make Memory Devices  Positive feedback loops is a general strategy for cell memory, maintenance of heritable patters of transcription.  Gene regulatory proteins that establish the body plan activates their own transcription --> create positive feedback loop to promote synthesis ---> repress transcription of other regulatory proteins  Interact with each other's synthesis, create sophisticated pattern of inherited behavior Transcription Circuits Allow the Cell to Carry Out Logic Operations  Certain types of regulatory circuit arrangement are found over and over again  Positive and negative feedback loops are common in all cells o Positive: provide simple memory device o Negative: keep the expression of a gene close to a standard level regardless of variation in biochemical conditions inside a cell  Repressor protein above critical value, transcription of its own gene occurs at low rate  Repressor protein below critical value, transcription occurs at high rate --> concentration of the protein close to critical value  Adjustment take time, so abrupt change will cause disturbance of gene expression that is strong but transient (Negative feedback loop --> detect sudden change)  Delay in feedback loop cause spontaneous oscillations in the expression of the gene  Two or more genes, complex range of control circuits and behavior  Example flip flop device ( virus lambda, repressor and Cro)  Feed Forward loop: serve as a filter, respond to signals that are prolonged but disregard those that are
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