Genetics Ch 15 Gene Regulation in Eukaryotes via Translation and Transcription

C24. What is DNA methylation? When we say that DNA methylation is heritable, what do we mean? How is it passed from a mother cell to a daughter cell?

C24. DNA methylation is the attachment of a methyl group to a base within the DNA. In many eukaryotic species, the attachment occurs on cytosine at a CG sequence. After de novo methylation has occurred, it is passed from mother cell to daughter cell. Because DNA replication is semiconservative, the newly made DNA contains one strand that is methylated and one that is not. DNA methyltransferase recognizes this hemimethylated DNA and methylates the cytosine in the unmethylated DNA strand; this event is called maintenance methylation.

C6. Transcription factors usually contain one or more motifs that play key roles in their function. What is the function of each of the following motifs? A. Helix-turn-helix B. Zinc finger C. Leucine zipper

A. DNA binding B. DNA binding C. Protein dimerization

C5. Is each of the following statements true or false? A. An enhancer is a type of regulatory element. B. A core promoter is a type of regulatory element. C. Regulatory transcription factors bind to regulatory elements. D. An enhancer may cause the down regulation of transcription.

A. True. B. False. C. True. D. False, it causes up regulation.

C1. Discuss the common points of control in eukaryotic gene regulation.

C1. See Figure 15.1.

C10. Explain how phosphorylation affects the function of the CREB protein.

C10. Phosphorylation of the CREB protein causes it to act as a transcriptional activator. Unphosphorylated CREB protein can still bind to a CRE, but it does not stimulate transcription via CBP.

C11. A particular drug inhibits protein kinase A, which is responsible for phosphorylating the CREB protein. How would this drug affect the following events? A. The ability of the CREB protein to bind to a CRE B. The ability of extracellular hormones to enhance cAMP levels C. The ability of the CREB protein to stimulate transcription D. The ability of the CREB protein to dimerize

C11. A. No effect. B. No effect. C. It would be inhibited. D. No effect.

C15. The DNA-binding domain of each CREB protein subunit recognizes the sequence 5′-TGACGTCA-3′. Due to random chance, how often would you expect this sequence to occur in the human genome, which contains approximately 3 billion base pairs? Actually, only a few dozen genes are activated by the CREB protein. Does the value of a few dozen agree with the number of random occurrences expected in the human genome? If the number of random occurrences of the sequence in the human genome is much higher than a few dozen, provide at least one explanation why the CREB protein is not activating more than a few dozen genes.

C15. There are four types of bases (A, T, G, and C), and this CRE sequence contains 8 bp, so according to random chance, it should occur every 48 bp, which equals every 65,536 bp. If you divide 3 billion by 65,536, this sequence is expected to occur approximately 45,776 times. This is much greater than a few dozen. There are several reasons why the CREB protein does not activate over 45,000 genes. 1. To create a functional CRE, there needs to be two of these sequences close together, because the CREB protein functions as a homodimer. 2. CREs might not be near a gene. 3. The conformation of chromatin containing a CRE might not be accessible to binding by the CREB protein.

C2. Discuss the structure and function of regulatory elements. Where are they located relative to the core promoter?

Regulatory elements are relatively short DNA sequences that are recognized by regulatory transcription factors. After a regulatory transcription factor binds to a regulatory element, it will affect the rate of transcription, either activating it or repressing it, depending on the action of the regulatory protein. Regulatory elements are typically located in the upstream region near the core promoter, but they can be located almost anywhere (i.e., upstream and downstream) and even quite far from the promoter.

C7. The binding of small effector molecules, protein-protein interactions, and covalent modifications are three common ways to modulate the activities of transcription factors. Which of these three mechanisms are used by steroid receptors and by the CREB protein?

Steroid receptors: binding of an effector molecule and protein-protein interactions; CREB protein: covalent modification and protein-protein interactions.

C3. List and describe three general ways that the functions of transcription factors can be modulated.

Transcription factor modulation refers to different ways that the function of transcription factors can be regulated. The three general ways are the binding of an effector molecule, protein-protein interactions, and covalent modifications.

C4. What are the functions of activator proteins and repressor proteins in transcription? Explain how these proteins work at the molecular level.

Transcriptional activation occurs when a regulatory transcription factor binds to a response element and activates transcription. Such proteins, called activators, may interact with TFIID and/or mediator to promote the assembly of RNA polymerase II and general transcription factors at the promoter region. They can also alter the structure of chromatin so that RNA polymerase II and transcription factors are able to gain access to the promoter. Transcriptional inhibition occurs when a regulatory transcription factor inhibits transcription. Such a repressor also may interact with TFIID and/or mediator to inhibit RNA polymerase II.