Control of Gene Expression in Eukaryotes

1. Control of Gene Expressionin Eukaryotes Chapter 18

2. Control of Gene Expression • More complex in eukaryotes than in prokaryotes • Creates different cell types, arranges them into tissues, and coordinates their activity • There are five points for control of gene expression in eukaryotes

4. Structural Control • Eukaryotic DNA must undergo physical changes before transcription can take place • nucleosomes—DNA wrapped twice around eight positively charged histone proteins

5. Structural Control • DNA must uncoil to transcribe • Required for polymerase to bind • Histone acetyl transferases (HATs) catalyze the acetylation and methylation of histones • Decondenses the chromatin and allows gene expression • Histone deacetylases (HDACs) remove the acetyl groups

6. Structural Control

7. Regulatory Sequences and Regulatory Proteins • Found upstream of the open reading frame • Promoter is the site where RNA polymerase bind • Regulatory proteins called promoter-proximal elements have sequences unique to specific genes

8. Enhancers • Regulatory sequences that can influence gene expression from a long distance • Upstream, downstream, or within the gene they regulate • Function in either orientation and can be moved to a different location of the same chromosome

9. Enhancers

10. Enhancers • Specific regulatory proteins found in these differentiated tissues must bind to regulatory elements found on the chromosome to regulate gene expression • Silencers similar to enhancers • Repress rather than activate gene expression.

11. Enhancers

12. Regulation of Transcription

13. Regulation of Initiation of Translation • Two classes of proteins bind to regulatory sequences: • basal transcription factors associate with the core transcription complex and the promoter sequence • regulatory transcription factors bind to enhancers and silencers • Coactivators are additional proteins involved in initiating transcription

14. Transcription initiation in eukaryotic cells • Step 1: Regulatory transcription factors recruit the chromatin-remodeling complex and HATs • Step 2: Chromatin remodeling results in loosening of the chromatin structure to expose the promoter

15. Transcription initiation in eukaryotic cells • Step 3. Additional regulatory transcription factors bind enhancers and promoter-proximal elements and recruit basal transcription factors to assemble at the promoter, forming the basal transcription complex. • Step 4. The basal transcription complex recruits RNA polymerase to form the initiation complex

17. Post-Transcriptional Control • Splicing mRNAs in various ways • Altering the rate at which translation is initiated • Modifying the life span of mRNAs and proteins after translation has occurred • Different exons are spliced together to produce different mature mRNAs • Make different proteins

18. Alternative Splicing

19. Alternative Splicing • Regulated by cell-type-specific proteins that regulate the spliceosome • At least 35% of human genes undergo alternative splicing. • Although we have only around 40,000 genes, it is anticipated that we express between 100,000 and 1 million different protein products.

20. Translational Control

21. Transcriptional Control in the Cytoplasm • Stability of mRNAs in the cytoplasm is highly variable • Some are degraded rapidly, while others are quite stable • Factors in the cytoplasm may also bind mRNAs to block their translation until needed • Can be slowed or stopped by phosphorylation (activated or deactivated)

22. Signal Transducers and Activators of Transcription • (STATs) are an example of post- translational regulation via protein phosphorylation

23. Cancer and Defects in Gene Regulation • Results from uncontrolled cell growth and is often the result of mutation • Due to mutagens • Cancer often results from mutations in genes that • (1) stop or slow the cell cycle • Or (2) trigger cell growth and division

24. Cancer • Tumor Suppressor Genes • Slow or stop the cell cycle • When their activity is lost cells are released from this negative control of the cell cycle. • Proto-oncogenes- Genes that trigger cell division are known as • Mutations that express these genes abnormally convert proto-oncogenes into oncogenes