1. Gene Regulation, Part 1 Lecture 15 Fall 2008

2. Metabolic Control in Bacteria Regulate enzymes already present –Feedback Inhibition –Fast response Control production of enzymes –Regulates transcription –Longer-term response 1 Fig. 18.2

3. Metabolic Control in Bacteria Operon –Unit of genetic function, found in bacteria and phages, consisting of an operator, promoter & coordinately regulated cluster of genes whose products function in a common pathway 2

4. Metabolic Control in Bacteria Promoter –Specific area of DNA that designates the start of a gene –Where RNA polymerase binds Operator –Sequence of nucleotides near the start of an operon to which an active repressor can attach –On-off “switch” for the cluster of genes 3 Fig. 18.3

5. Metabolic Control in Bacteria Regulatory gene –Gene that codes for a protein that controls the transcription of another gene or group of genes Repressor –Protein that inhibits gene transcription –Binds to operator & prevents RNA polymerase from attaching to promoter 4 Fig. 18.3

6. Metabolic Control in Bacteria Repressors –Specific to an operator of a specific gene Regulatory genes expressed continuously, but at low rate –On-off regulated by concentration of repressors –Repressors are allosteric proteins Active & inactive form Corepressors –Small molecules that cooperate with repressor to turn off transcription 5

7. Metabolic Control in Bacteria Repressible Operon –Operon where transcription is normally “on”, but that can be inhibited (repressed) –E.g., trp operon (tryptophan) 6 Fig. 18.3

8. Metabolic Control in Bacteria trp operon trp repressor synthesized in an inactive form Tryptophan acts as corepressor 7 Fig. 18.3

9. Metabolic Control in Bacteria Inducible operon –Operon where transcription is normally “off”, but that can be stimulated (induced) –E.g., lac operon (lactose) lac repressor synthesized in active form Binds to operator Prevents RNA Polymerase from binding 8 Fig. 18.4

10. Metabolic Control in Bacteria Inducer binds to lac repressor Inducer: specific small molecule that binds to repressor protein and changes its shape –Repressor inactivated –Releases/does not bind with operator –Transcription occurs 9 Fig. 18.4

11. Negative and positive gene regulation Negative gene regulation –Operons switched off by active form of a repressor protein –E.g., lac and trp operons Positive gene regulation –Regulatory protein interacts directly with the genome to switch transcript on 10

12. Negative and positive gene regulation Lactose metabolism only occurs when glucose concentrations low Catabolite activator protein (CAP) & cyclic AMP (cAMP) CAP is activator –Protein that binds to DNA and stimulates transcription of a gene cAMP concentration high when glucose concentration low cAMP activates CAP 11 Fig. 18.5

13. Negative and positive gene regulation CAP attaches to CAP- binding site on promoter Increases affinity of RNA polymerase for promoter Activators increase the rate of transcription –As long as lactose is present, transcription can still occur 12 Fig. 18.5