1. CHAPTER 18  REGULATION OF GENE EXPRESSION 18.1  Bacterial regulation I. Intro A. Genes are controlled by an on/off “switch ” 1. If on, the genes can be transcribed 2. If off, the genes cannot be transcribed B. RNA polymerase has restricted access to DNA II. Operons: The basic concept A. Operator 1. The “switch ” that controls DNA transcription 2. A segment of DNA located within the promoter 3. May control 1 gene or several related genes

2. B. Operon 1. Operator + promoter + gene(s) C. Operating the switch 1. Repressor (“switch ” protein) a. Attached to operator= operon repressed (turned off) Not attached= operon not repressed (turned on) b. Operator specific

4. c. Regulatory genes 1. Genes located away from operon that code for “switch ” proteins 2. Continuously making the proteins III. Repressible & inducible operons: Two types of negative gene regulation A. Repressible operons 1. Operons are turned on by default a. No repressor attached to operator b. RNA polymerase can attach & transcribe c. To turn off a repressor protein attaches to operator 1. Blocks RNA polymerase attachment 2. Reversible 3. Allosteric protein a. Active & inactive shapes b. Inactive state by default 1. Corepressor needed to activate

5. 2. Example a. E coli & AA tryptophan  trp operon 1. Metabolic pathway

6. 2. Gene regulation a. trpR = regulatory gene 1. Codes for inactive repressor a. Corepressor (tryptophan) attaches to repressor making it active thus operator switch off

7. B. Inducible operons 1. Operons are turned off by default a. Repressor attached to operator b. To turn on an inducer bonds to repressor inactivating it 1. Allosteric protein a. Active state default 2. Example a. lac operon

8. IV. Cyclic AMP + CAP: A type of positive gene regulation A. Preferred energy source is glucose 1. Lactose if glucose is lacking B. Glucose present 1. Glycolysis proceeds as normal 2. Bacteria provided with ATP C. Glucose lacking/lactose present 1. Bacteria need to change energy source a. Need enzymes for lactose breakdown

9. 2. cAMP [ ] increases with a lack of glucose a. Activates CAP 1. An activator 2. Binds to promotor of lac operon a. Increases affinity of RNA polymerase for promotor of lac operon 1. Increases rate of transcription D. CAP directly stimulates gene expression 1. Positive regulation

10. V. Lac operon A. Under dual control 1. Negative control by lac repressor a. Determines whether lac operon is transcribed at all 2. Positive control by CAP a. Determines the rate of transcription

11. 18.2  Eukaryotic gene expression can regulate at any stage

12. I. Regulation of chromatin structure A. DNA is found in what state in non-dividing cells 1. Heterochromatin 2. Euchromatin

13. B. Chemical modifications of histones & DNA 1. Histone modification a. Heterochromatin occurs due to the histones bonding with neighboring nucleosomes 1. Chromatin becomes tightly compacted b. Histones Acetylation 1. Acetyl groups (-COCH 3 ) attach to histones 2. Heterochromatin loosens into euchromatin 3. DNA transcription can occur

14. 2. DNA Methylation a. Certain DNA bases become methylated b. Prevents transcription c. 1 potential cause for cell differentiation d. Can be passed on during cell division