Chapter 18 Regulation of Gene Expression PowerPoint® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Overview: Conducting the Genetic Orchestra • Prokaryotes and eukaryotes alter gene expression in response to their changing environment 2 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Bacteria often respond to environmental change by regulating transcription • Natural selection has favored bacteria that produce only the products needed by that cell • A cell can regulate the production of enzymes by feedback inhibition or by gene regulation • Gene expression in bacteria is controlled by the operon model 3 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Precursor Feedback inhibition trpE gene Regulation of a metabolic pathway Enzyme 1 trpD gene Regulation of gene expression Enzyme 2 trpC gene trpB gene Enzyme 3 trpA gene Tryptophan (a) Regulation of enzyme activity (b) Regulation of enzyme production Operons: The Basic Concept • A cluster of functionally related genes can be under coordinated control by a single on-off “switch” • The regulatory “switch” is a segment of DNA called an operator usually positioned within the promoter • An operon is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control 5 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Figure 18.UN01 Operon Promoter Genes B C A Operator RNA polymerase A B C Polypeptides 6 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings • The operon can be switched off by a protein repressor • The repressor prevents gene transcription • The repressor is the product of a separate regulatory gene 7 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Repressible and Inducible Operons: Two Types of Negative Gene Regulation • A repressible operon is one that is usually on; binding of a repressor to the operator shuts off transcription • An inducible operon is one that is usually off; a molecule called an inducer inactivates the repressor and turns on transcription 8 © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings ©Copyright 2011 Pearson Education, Inc. EXAMPLE: The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose 9 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Eukaryotic gene expression can be regulated at any stage • All organisms must regulate which genes are expressed at any given time • In multicellular organisms gene expression is essential for cell specialization 10 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Differential Gene Expression • Almost all the cells in an organism are genetically identical • Differences between cell types result from differential gene expression, the expression of different genes by cells with the same genome • Errors in gene expression can lead to diseases including cancer • Gene expression is regulated at many stages 11 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Signal NUCLEUS Chromatin Chromatin modification DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Intron RNA processing Tail Cap mRNA in nucleus Transport to cytoplasm CYTOPLASM CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypeptide Protein processing Active protein Degradation of protein Transport to cellular destination Cellular function Regulation of Chromatin Structure • Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression Regulation of Transcription Initiation • Chromatin-modifying enzymes provide initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery 14 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Animation: DNA Packing 15 Right-click slide / select “Play” © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings ©Copyright 2011 Pearson Education, Inc. Histone tails Amino acids available for chemical modification DNA double helix A simple model of histone tails and the effect of histone acetylation Nucleosome (end view) (a) Histone tails protrude outward from a nucleosome Acetylated histones Unacetylated histones (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings 16 A eukaryotic gene and its transcript Enhancer (distal control elements) Poly-A signal sequence Termination region Proximal control elements Exon Intron Exon Intron Exon DNA Upstream Downstream Promoter Primary RNA 5 transcript Transcription Exon Intron Exon Intron Exon RNA processing Cleaved 3 end of primary transcript Poly-A signal Intron RNA Coding segment mRNA 3 5 Cap 5 UTR Start codon Stop codon 3 UTR Poly-A tail Mechanisms of Post-Transcriptional Regulation • Transcription alone does not account for gene expression • Regulatory mechanisms can operate at various stages after transcription • Such mechanisms allow a cell to fine-tune gene expression rapidly in response to environmental changes 18 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Initiation of Translation • The initiation of translation of selected mRNAs can be blocked by regulatory proteins • Alternatively, translation of all mRNAs in a cell may be regulated simultaneously • For example, translation can be simultaneously activated in an egg following fertilization 19 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Protein Processing and Degradation • After translation, various types of protein processing, including cleavage and the addition of chemical groups, are subject to control • Proteasomes are giant protein complexes that bind protein molecules and degrade them Proteasome and ubiquitin to be recycled Ubiquitin Proteasome Protein to be degraded Ubiquitinated protein Protein entering a proteasome Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Protein fragments (peptides) 20 A program of differential gene expression leads to the different cell types in a multicellular organism • During embryonic development, a fertilized egg gives rise to many different cell types • Cell types are organized successively into tissues, organs, organ systems, and the whole organism • Gene expression orchestrates the developmental programs of animals 21 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings A Genetic Program for Embryonic Development • The transformation from zygote to adult results from cell division, cell differentiation, and morphogenesis From fertilized egg to animal: What a difference four days makes (a) Fertilized eggs of a frog 22 (b) Newly hatched tadpole Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Figure 18.19a Key developmental events in the life cycle of Drosophila Head Thorax Abdomen 0.5 mm Dorsal BODY AXES Anterior Left Right Posterior Ventral (a) Adult 23 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings • Cell differentiation is the process by which cells become specialized in structure and function • The physical processes that give an organism its shape constitute morphogenesis • Differential gene expression results from genes being regulated differently in each cell type 24 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Sequential Regulation of Gene Expression During Cellular Differentiation • In the process called induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells • Thus, interactions between cells induce differentiation of specialized cell types • Determination commits a cell to its final fate • Determination precedes differentiation 25 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Abnormal pattern formation in Drosophila Eye Leg Antenna Wild type Mutant ? ? ? ? ? ? ?
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