Chapter 18: Regulation of Gene Expression

1. Chapter 18: Regulation of Gene Expression

2. Essential Knowledge 2.e.1 – Timing and coordination of specific events are necessary for the normal development of an organism, and these events are regulated by a variety of mechanisms (18.2-18.4). 3.b.1 – Gene regulation results in differential gene expression, leading to cell specialization (18.1-18.3). 3.b.2 – A variety of intercellular and intracellular signal transmissions mediate gene expression (18.1-18.4). 4.a.3 – Interactions between external stimuli and regulated gene expression result in specialization of cells, tissues, and organs (18.4).

3. Bacterial Regulation of Transcription • Some bacteria can regulate their gene expression based on their surroundings • E. coli needs tryptophan to survive; if it isn’t getting trp from its environment (such as the human colon), then it makes its own • When the host is ingesting enough trp for the E. coli, the bacteria inhibits enzyme activity thereby shutting down the synthesis of trp and conserving energy.

4. Operons Fig. 18.2, page 352 An operon includes the operator (which controls the access of RNA polymerase to the genes), the promoter (a site where RNA polymerase can bind to DNA and begin transcription), and all the genes they control

5. Operon Function • Using trp synthesis as an example: • The trp operon is turned on meaning that RNA polymerase can bind to the promoter and transcribe the genes of the operon • The trp repressor switches the operon off, and the repressor binds to the operator blocking attachment of RNA polymerase to the promoter preventing gene transcription • Fig. 18.3, page 353

6. Human Genome 3 billion base pairs ~30,000 genes Total of almost 3 FEET of DNA in each and every cell in our bodies

7. Questions? With so much DNA in a cell, how is it organized or packaged? How is the expression of the DNA controlled?

8. Microscopic Levels 1. Nucleosomes 2. Chromatin Fibers 3. Looped Domains 4. Chromosomes Focus on #1 & #4

10. Nucleosomes "Beads on a String” DNA wound on a protein core Packaging for DNA Controls transcription

11. Protein Core Two molecules of four types of Histoneproteins H1- 5th type of Histone protein attaches the DNA to the outside of the core

12. Chromosomes Large units of DNA/chromatin/proteins Appear only during cell division (after Interphase) Similar to "Chapters" in the Book of Life

13. Chromosome Regions 1. Heterochromatin - highly condensed chromatin; areas that are nottranscribed 2. Euchromatin - less condensed chromatin; areas of activetranscription

14. Molecular Level Organization 1. Repetitive Sequences 2. Satellite DNA 3. Interspersed Repetitive DNA 4. Multigene Families

15. Result • Give regions of the DNA different densities • Linked to some genetic disorders. • Ex. - Fragile X Syndrome • Huntington’s disease

16. Multigene Families A collection of identical or very similar genes From a common ancestral gene. May be clustered or dispersed in the genome

17. Identical Families • Identical genes for the same protein • Ex: Ribosomal Protein and rRNA • Result - Many copies of ribosomespossible • Most common gene in DNA

18. Nonidentical Families Related clusters of genes that are nearly identical in their base sequences. Ex: Globin Genes

19. Pseudogene Gene with sequences very similar to real genes, but lack promoter sites Are not transcribed into proteins Possible proof of transpositions?

20. Genome Plasticity Changes in the ways a gene can be expressed Seen only in somatic cells Have major effects on gene expression within particular cells and tissues

21. Types of Expression 1. Gene Amplification 2. Selective Gene Loss 3. Genomic Rearrangements

22. 1. Gene Amplification The selective replication of certain genes Ex: rRNA genes in eggs Result - many copies of rRNA for making ribosomes

23. 2. Selective Gene Loss Loss of genes or chromosomes in some tissues during development Result - DNA (genes) lost and not expressed

24. 3. Genomic Rearrangements • Shuffling of DNA areas (not from meiosis) • Ex: Transposonsretrotransposons antibody genes • Examples of Transposons: flower petals

25. Control of Gene Expression Complicated Process Many levels of control are possible Hint - students should understand several mechanisms of control (see slides to follow)

26. Main Control Levels 1. Nucleus - those inside the nuclear membrane 2. Cytoplasm - those that occur in the cytoplasm

28. Nucleus Level 1. Extra-Cellular Signals (Chapter 11 – Cell communication) 2. Chromatin Modifications 3. Transcriptional Control 4. Posttranscriptional Control

29. Chromatin Modifications DNA Methylation HistoneAcetylation Gene rearrangements Gene amplification

30. DNA Methylation Addition of methyl groups (-CH3) to DNA bases Result - long-term shut-down of DNA transcription Ex: Barr bodies

31. Histone Acetylation Attachment of acetyl groups (-COCH3) to AAs in histones Result - DNA held less tightly to the nucleosomes, more accessible for transcription

32. Transcriptional Control • Ex: Enhancers • Areas of DNA that increase transcription. • Ex: DNA-Binding Domains • Proteins that bind to DNA and regulate transcription • Ex: regulatory RNA. • Small RNA molecules that are not translated • Usually interact with DNA • Result - genes are more (or less) available for transcription.

33. Posttranscriptional Control 1. RNA Processing • Ex - introns and exons 2. RNA Transport • moving the mRNA into the cytoplasm 3. RNA Degradation • breaking down old mRNA

34. Cytoplasm Level of Control 1. Translation 2. Polypeptide Changes

35. Translation Control • Regulated by the availability of initiation factors • Availability of tRNAs, AAs and other protein synthesis factors • (Review Chapter 17)

36. Polypeptide Changes • Changes to the protein structure after translation • Ex: Cleavage • Modifications • Activation • Transport • Degradation

37. Gene Expression and Cancer Cancer - loss of the genetic control of cell division Balance between growth-stimulating pathway (accelerator) and growth-inhibiting pathway (brakes)

39. Proto-oncogenes Normal genes for cell growth and cell division factors Genetic changes may turn them into oncogenes (cancer genes) Ex: Gene Amplification, Translocations, Transpositions, Point Mutations

40. Tumor-Suppressor Genes • Genes that inhibit cell division • Ex - p53, p21

41. Cancer Examples RAS - a G protein When mutated, causes an increase in cell division by over-stimulating protein kinases Several mutations known

42. Cancer Examples p53 - involved with several DNA repair genes and “checking” genes. When damaged (e.g. cigarette smoke), can’t inhibit cell division or cause damaged cells to apoptose.

43. Carcinogens • Agents that cause cancer • Ex: radiation, chemicals • Most work by altering the DNA, or interfering with control or repair mechanisms • See Chapter 17 for more on this!

44. Multiple Hit Hypothesis • Cancer is the result of several control mechanisms breaking down • Ex: Colorectal Cancer requires 4 to 5 mutations before cancer starts

45. Colorectal Cancer

46. Summary Recognize the operon model for gene regulation in prokaryotes. Identify different mechanisms of eukaryotic gene expression control. Recognize the roles of RNA in controlling gene expression. Recognize examples of differential gene expression in multicellular organisms. Recognize that cancer is caused by changes in gene regulation.