Chapter 19 Genetic Regulation of the Eukaryotic Genome. A. Bergeron AP Biology PCHS

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1 Chapter 19 Genetic Regulation of the Eukaryotic Genome A. Bergeron AP Biology PCHS

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3 Do Now - Eukaryotic Transcription Regulation The diagram below shows five genes (with their enhancers) from the genome of a certain species. Imagine that orange, blue, green, black, red, and purple activator proteins exist that can bind to the appropriately color-coded control elements in the enhancers of these genes. Enhancer Promoter Gene 1 Gene 2 Gene 3 Gene 4 Gene 5

4 Do Now - Eukaryotic Transcription Regulation Imagine that genes 1, 2, and 4 code for nerve-specific proteins, and genes 3 and 5 are skin-specific. Which activators would have to be present in each cell type to ensure transcription of the appropriate genes? Enhancer Promoter Gene 1 Gene 2 Gene 3 Gene 4 Gene 5

5 Control of Eukaryotic Gene Expression Although there are approximately 30,000 human genes in the genome, a cell will not express all of these genes at the same time What can a eukaryotic cell do to regulate gene expression? 1. Pre-transcriptional regulation a. DNA methylation b. Histone acetylation/chromatin remodeling 2. Post-transcriptional modification! a. Removal of introns/exon splicing! b. Nuclear transport of mrna! c. RNA interference (RNAi) 3. Post-translational regulation! a. Degradation of protein via ubiquitin and proteasome

6 DNA Coiling - Formation of a Chromosome Nucleosome Composed of positively charged histone proteins that interact with negatively charged DNA molecules 150 base pairs of DNA wrap around each histone complex

7 Chromatin Packaging Nucleosome Solenoid Loops Rosettes DNA Packaging

8 Interaction Between DNA and Histone Protein Basic side groups (positively charged) are attracted to the negatively charged phosphate groups found on DNA The electrostatic interactions produce the structure of the nucleosome seen above

9 Forms of Chromatin in a Eukaryotic Cell There are two types of chromatin found within the eukaryotic genome: heterochromatin and euchromatin Heterochromatin is not expressed due to its high level of packaging and consequent inaccessibility to the transcription initiation complex Euchromatin is expressed because it has been unpackaged and is accessible to RNA polymerase and transcription factors

10 How to Turn a Eukarytoic Gene On

11 Other Mechanisms to Regulate Eukaryotic Transcription

12 Other Mechanisms to Regulate Eukaryotic Transcription

13 Other Mechanisms to Regulate Eukaryotic Transcription The combination of enhancer DNA elements, transcription factors, and RNA polymerase II form the eukaryotic transcription complex which turns on gene expression Gene transcription could be regulated at any or all of these levels in a particular type of cell

14 Do Now - Effect of Hormones on Gene Expression Prostate cells usually require testosterone and other androgens to survive. But some prostate cancer cells thrive despite treatments that eliminate androgens. One hypothesis states that estrogen, often considered a female hormone, may be activating genes normally controlled by an androgen in these cancer cells. Describe one or more experiments to test this hypothesis. Be sure to identify any controls that would be required to validate the results of your experiment.

15 DNA Methylation The precise regulation of gene expression by DNA methylation is still being worked out Methylated cysteine nucleotides disrupt interactions between transcription factor proteins, promoter sequences and RNA polymerase DNA methylation may also affect the degree to which chromatin can be packaged within the nucleus

16 Ubiquitin-targeted Destruction of Cellular Proteins Translation can be controlled by regulating whether or not the ribosomal subunits are able to bind to the mrna What can the cell do if the protein has already been translated? Answer: The Proteasome! (A Cellular Garbage Can!) Proteins targeted for destruction are first ubiquitinated -Ubiquitin is a small protein that marks a protein for destruction Ubiquintinated proteins bind to the proteasome, are unfolded, and hydrolyzed into small peptides which are recycled within the cell

17 RNA Interference (RNAi - Nature.com) The process of RNAi begins via the normal transcription process Short RNA's can lead to silencing the expression of genes that contain complementary sequences in their mrna A complex of double-stranded RNA is cleaved into short fragments (sirna - short interfering RNAs) of basepairs in length by the enzyme Dicer. The sirna's bind to the RISC (RNAinduced silencing complex).

18 RNA Interference One of the strands of sirna is degraded and the remaining single-stranded sirna, which is complexed with the RISC can then bind to complementary mrna. If a perfect or near perfect match, the mrna is cleaved.

19 Structure of a Transposon Transposon = a mobile genetic element Transposons provides certain organisms with a unique way of creating genetic variations within a population