iga11e_ch12

Chapter Introduction

Regulation of Gene Expression in Eukaryotes

431

Regulation of Gene

Expression in

Eukaryotes

CHAPTER

LEARNING OUTCOMES

After completing this chapter, you will be able to

Compare and contrast the molecular mechanisms of gene regulation in eukaryotes and bacteria.
Explain how eukaryotes generate many different patterns of gene expression with a limited number of regulatory proteins.
Discuss the involvement of chromatin in eukaryotic gene regulation.
Describe the concept of epigenetic marks, and discuss how these can work in both DNA and proteins.
Compare and contrast the roles played by RNA molecules in repressing eukaryotic gene expression.

Xist RNA (labeled by a red rhodamine dye) covers one of the two copies of the X chromosome. The expression of Xist will lead to the chromosome’s inactivation. The image is from an RNA fluorescent in situ hybridization (FISH) experiment performed on a metaphase chromosome spread taken from a female fibroblast cell line.

[J. T. Lee et al., “Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome,” Genes Dev., 23 (16), 2009, 1831–1842, Fig. 2. © Cold Spring Harbor Laboratory Press. Photography by Jeannie Lee.]

OUTLINE

12.1	Transcriptional regulation in eukaryotes: an overview
12.2	Lessons from yeast: the GAL system
12.3	Dynamic chromatin
12.4	Activation of genes in a chromatin environment
12.5	Long-term inactivation of genes in a chromatin environment
12.6	Gender-specific silencing of genes and whole chromosomes
12.7	Post-transcriptional gene repression by miRNAs

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The cloning of Dolly, a sheep, was reported worldwide in 1996 (Figure 12-1). Dolly developed from adult somatic nuclei that had been implanted into enucleated eggs (eggs with the nuclei removed). More recently, cows, pigs, mice, and other mammals have been cloned as well with the use of similar technology. The successful cloning of Dolly was a great surprise to the scientific community because gamete (sperm and egg cells) formation was known to include sex-specific modifications to the respective genomes that resulted in sex-specific patterns of gene expression. Dolly is symbolic of how far we have progressed in understanding aspects of eukaryotic gene regulation such as the global control of gene expression exemplified by gamete development. However, for every successful clone, including Dolly, there are many more, perhaps hundreds of embryos that fail to develop into viable progeny. The extremely high failure rate underscores how much remains to be deciphered about eukaryotic gene regulation.

Figure 12-1: The first cloned mammal

Figure 12-1: The first cloned mammal was a sheep named Dolly.

In this chapter, we will examine gene regulation in eukaryotes. In many ways, our look at gene regulation will be a study of contrasts. In Chapter 11, you learned how the activities of genetic switches in bacteria were often governed by single activator or repressor proteins and how the control of sets of genes was achieved by their organization into operons or by the activity of specific factors. Initial expectations were that eukaryotic gene expression would be regulated by similar means. In eukaryotes, however, most genes are not found in operons. Furthermore, we will see that the proteins and DNA sequences participating in eukaryotic gene regulation are more numerous. Often, many DNA-binding proteins act on a single switch, with many separate switches per gene, and the regulatory sequences of these switches are often located far from promoters. A key additional difference between bacteria and eukaryotes is that the access to eukaryotic gene promoters is restricted by chromatin. Gene regulation in eukaryotes requires the activity of large protein complexes that promote or restrict access to gene promoters by RNA polymerase. This chapter will provide an essential foundation for understanding the regulation of gene expression in time and space that choreographs the process of development described in Chapter 13.