Regulation of Gene Expression in Eukaryotes Chapter 18 Regulation of Gene Expression in Eukaryotes Copyright © 2009 Pearson Education, Inc.

Regulation of Gene Expression in Eukaryotes Can Occur at Many Different Levels Figure 18-1 Various levels of regulation that are possible during the expression of the genetic material. Figure 18.1

Cis-Acting Sites Figure 18-6 Transcription of eukaryotic genes is controlled by regulatory elements directly adjacent to the gene (promoters) and by others located at a distance (enhancers and silencers). Figure 18.6

Examples of Cis-Acting Sites Figure 18-7 Organization of the transcription regulatory regions in several genes expressed in eukaryotic cells, illustrating the variable nature, number, and arrangement of controlling elements. Figure 18.7

Human Metallothionein IIA Gene Figure 18-10 The human metallothionein IIA gene promoter and enhancer regions, containing multiple cis-acting regulatory sites. The transcription factors controlling both basal and induced levels of MTIIA transcription are indicated below the gene, with arrows showing their binding sites. Figure 18.10

Functional Domains Trans-activating or Trans-Repression Domains DNA binding domains Helix-turn-helix Zinc fingers Basic leucine zippers (bZIP)

Helix-Turn-Helix Figure 18-11 A helix–turn–helix or homeodomain in which (a) three planes of the -helix of the protein are established, and (b) these domains bind in the grooves of the DNA molecule. Figure 18.11

Zinc Fingers Figure 18-12 (a) A zinc finger in which cysteine and histidine residues bind to a Zn2+ atom. (b) This loops the amino acid chain out into a fingerlike configuration. Figure 18.12

Leucine Zipper Figure 18-13 (a) A leucine zipper is the result of dimers from leucine residue at every other turn of the -helix in facing stretches of two polypeptide chains. (b) When the -helical regions form a leucine zipper, the regions beyond the zipper form a Y-shaped region that grips the DNA in a scissorlike configuration. Figure 18.13

Transcription Initiation Figure 18-14 The assembly of transcription factors required for the initiation of transcription by RNA polymerase II. Figure 18.14

Enhancers Figure 18-15 Formation of DNA loops allows factors that bind to enhancers at a distance from the promoter to interact with regulatory proteins in the transcription complex and to maximize transcription. Figure 18.15

The GAL Gene System in Yeast Figure 18-16 Model of GAL1 and GAL10 UAS structures showing the binding sites for the Gal4p positive regulator and their interaction with the Gal80p negative regulator. Induction is shown as the structure of the Gal80p becomes altered, exposing the activation domain of Gal4p. Figure 18.16

Posttranscriptional Gene Regulation Alternative splicing mRNA stability Translation Protein stability

Posttranscriptional Gene Regulation Alternative splicing Control of mRNA stability Control of translation Control of protein stability

Alternative Splicing Figure 18-18 Alternative splicing of the CT/CGRP gene transcript. The primary transcript, which is shown in the middle of the diagram, contains six exons. The primary transcript can be spliced into two different mRNAs, both containing the first three exons but differing in their final exons. The CT mRNA contains exon 4, with polyadenylation occurring at the end of the fourth exon. The CGRP mRNA contains exons 5 and 6, and polyadenylation occurs at the end of exon 6. The CT mRNA is produced in thyroid cells. After translation, the resulting protein is processed into the calcitonin peptide. In contrast, the CGRP mRNA is produced in neuronal cells, and after translation, its protein product is processed into the CGRP peptide. Figure 18.18

Control of mRNA Stability All mRNAs degrade at some point Many genes are controlled by how long the mRNA is present Pathways to degradation Shorten the polyA tail Remove the 7-methylguanosine cap Endonucleases

Control of Translation Figure 18-22 Posttranscriptional regulation of (a) ferritin and (b) transferrin receptor gene expression. Iron regulatory proteins bind to the IRE stem-loop structure in both ferritin and transferrin receptor mRNAs. In the absence of free iron, the iron regulatory proteins inhibit translation of ferritin mRNAs but stabilize transferrin receptor mRNAs. In the presence of free iron (shown here as dark red circles), the iron regulatory proteins dissociate from the IREs, resulting in increased translation of ferritin and destabilization of transferrin receptor mRNA. Figure 18.22