Regulation of Gene Activity and Gene Mutations

1. Regulation of Gene Activity and Gene Mutations Mader- Chapter 15

2. Prokaryotic Regulation • The Operon Model • Structural genes are controlled by upstream operator DNA than can bind a repressor molecule which prohibits RNA polymerase from binding to the promoter region of DNA

3. Repressible vs. Inducible Operons-Two types of negative gene control trpOperon • Repressible operon (on unless turned off) • The gene for anabolizing tryptophan is turned off in the presence of the amino acid tryptophan lacOperon • Inducible operon (off unless turned on) • The gene for catabolizing lactose is turned on in the presence of the sugar lactose Both are switched off by active forms of the repressor molecule so therefore these are both examples of negative gene control Virtual Cell lacOperon Movie

4. Positive Gene Regulation through “CAP” Catabolic activating protein • When glucose levels are low then cAMP is high • cAMPacivates CAP • CAP binds to promoter and enhances binding of RNA Polymerase lacOperon

5. Eukaryotic Regulation 5 Levels of Eukaryotic Gene Regulation • Chromatin Structure-Does RNA Polymerase have access to the gene • Transcriptional Control-transcription factors, activators, and the presence or absence of transposons • Posttranscriptional Control-RNA processing • Translational Control- Does tranlation take place and for how long? • Post Translational Control- Activation of the protein itself

6. One of my X chromosomes is shut down through methylation in every cell… meow! Chromatin Structure Acetylation (-COCH3) opens up the DNA for transcription but Methylation (-CH3) of the tails shuts it down

7. An early mistake during mitosis incorrectly separates the X and Y chromosome creating an organism that is half male and half female! Odd cases of Bilateral Gynadromorphism

8. Transcriptional Control in Eukaryotes • Transcription Factors and Activators • Transcription Factors- There are many types… these proteins bind to the promoter and help RNA polymerase bind • Transcription Activators- bind to an upstream Enhancer region and also promote transcription Transposons “Jumping Genes” are noncoding sections of DNA that can also insert themselves into the structural gene and effectively turn them off

9. Post Transcriptional Control- mRNA Editing It is not well understood how cells determine which form of mature mRNA that they will make but it is clear that the one gene to one protein theory is simply untrue. It was found that one gene in Drosophilia is alternatively spliced ~17,500 different ways which all become cell surface proteins that identify placement of neurons in the organism

10. Translational Control • The 5’ methylated cap and the 3’ poly A tail determine “If” and “for how long” will translation occur. • Also, research is being done to discover how introns are feeding back to regulate translation of mRNA

11. Effects on mRNA by MicroRNAs and Small Interfering RNAs • miRNAs and siRNAs are very similar • Both begin double stranded and then degraded to single stranded • Both bind to mRNA of complimentary sequence to attract a degrading protein • Degradation of mRNA silences the gene

12. Post Translational Control • Lastly, cells control how long a protein will remain active. Cells have many proteases for degrading and breaking down old protein.

13. From zygote to tadpole to frog; How does this happen? • The unfertilized egg is not homogenous in respects to mRNA and proteins; these are known as cytoplasmic determinants that begin differentiation • Changing cells send signals to nearby cells causing change; this is termed induction • Positional information from steps 1 and 2 creates pattern formation of body axes by influencing homeotic genes