1. Lecture 8 Ch.7 (II) Eukaryotic Gene Regulation

2. Control of Gene Expression in Eukaryotes: an overview

4. Control at the level of chromatin and genome structure Epigenetic Inheritance: It is an unconventional finding. It goes against the idea that inheritance happens only through the DNA code that passes from parent to offspring. It means that a parent's experiences, in the form of epigenetic tags, can be passed down to future generations. ????????????????????????????????????????????????

5. Let’s understand what Epigenetics is Epigenetics is a system that turns our genes on and off. The process works by chemical tags, known as epigenetic marks, attaching to DNA and telling a cell to either use or ignore a particular gene. A common epigenetic mark is Methyl Group (-CH3). When DNA is methylated, proteins can’t bind, therefore gene is turned off.

6. Epigenetic Inheritance Previously, we thought epigenetic marks will be erased in primordial gene cells (PGC: a precursor to sperm and egg) from generation to generation. Certain epigenetic marks escape and make it through unchanged from parent to offspring.

7. How to prove it? Answer: 4 th Generation

8. Recent Research from Science http://science.sciencemag.org/content/339/61 18/448 http://science.sciencemag.org/content/339/61 18/448

9. Transcriptional Control in Eukaryotes

10. Co-activator and Co-repressor

11. Some proteins affect transcription without binding to DNA Coactivator -binds to and affects activator protein which binds to DNA -does not itself bind to DNA Corepressor -binds to and affects silencer/repressor protein which binds to DNA -does not itself bind to DNA

12. Mediator Protein Complex Composed of at least 30 subunits Similar size as RNA Polymerase Mediator is a coactivator Serves as a bridge between DNA-bound transcription activators, RNA Polymerase, and the general transcription factors.

13. A single transcription regulator can affect an entire organ Example: Ey in flies and Pax-6 in vertebrates is crucial for eye development.

14. Post-transcriptional Control Operates after RNA polymerases has bound to a gene’s promoter and started to synthesize RNA Examples: Alternative splicing

15. RNA editing A process in which the RNA sequence is modified. The two editing mechanisms include: site-specific deamination and guide RNA- directed insertion of uridine. site-specific deamination

16. RNA editing guide RNA-directed insertion of uridine in Mitochondria RNA

17. Riboswitches: short sequences of RNA that change their conformation when bound to small molecules such as metabolites

18. Untranslated Regions of mRNAs Can Control Their Translation 5’ capped mRNAs help protect the mRNA so it can find AUG *start code of translation. Repressors can bind to 5’ untranslated region to keep it from binding to ribosome, therefore, translation is not initiated. microRNA (miRNA) for example is found in both plants and animals. It is responsible fro 30% of all gene expression regulation.

19. miRNA Mature miRNA can form an RNA-induced silencing complex (RISC) with specialized proteins. RISC patrols the cytoplasm, searching for mRNA that are complementary to the miRNA it carries. Once a target mRNA forms base pairs with an miRNA, it is destroyed immediately. RISC can be reused once mRNA is completely degraded.

20. RISC Mechanism

22. RNA Interference: a defense mechanism RNAi is a biological process in which RNA molecules inhibit gene expression. For example: ds foreign RNA from viruses can be targeted for destruction. When an dsRNA attacks DICER (protein complex). It then slices dsRNA into smaller fragments called siRNA (small interfering RNA) RISC discards one strand of siRNA and uses another to search for complementary foreign RNA.

23. RNAi