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GENE REGULATION 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes • Early understanding of gene control Figure 11.1A Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Colorized SEM 7,000 – Came from studies of the bacterium Escherichia coli The lac Operon • In prokaryotes, genes for related enzymes – Are often controlled together in units called operons The Lac operon produces proteins responsible for lactose utilization – so the cell can use lactose So if you were a cell, and lactose was present, would you want these genes turned ON or OFF? Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings • Regulatory proteins bind to control sequences in the DNA and turn operons on or off in response to environmental changes Operon turned off (lactose absent) Regulatory gene OPERON Promoter Operator Lactose-utilization genes DNA mRNA Protein RNA polymerase cannot attach to promoter Active repressor Operon turned on (lactose inactivates repressor) DNA RNA polymerase bound to promoter mRNA Protein Lactose Figure 11.1B Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Inactive repressor Enzymes for lactose utilization Other Kinds of Operons • The trp operon – Is similar to the lac operon, but functions somewhat differently Promoter Operator Genes DNA Active repressor Active repressor Tryptophan Inactive repressor Inactive repressor Lactose Figure 11.1C lac operon Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings trp operon EUKARYOTIC GENE EXPRESSION 11.2 Differentiation yields a variety of cell types, each expressing a different combination of genes • In multicellular eukaryotes – Cells become specialized as a zygote develops into a mature organism Figure 11.2 Muscle cell Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Pancreas cells Blood cells Overview of Gene Regulation in Eukaryotes NUCLEUS DNA Packaging Chromosome DNA unpacking Other changes to DNA Gene Transcription Regulation Gene Transcription Exon RNA transcript Intron Addition of cap and tail Tail Splicing mRNA in nucleus Cap Flow through nuclear envelope mRNA in cytoplasm CYTOPLASM Breakdown of mRNA Translation Brokendown mRNA Post-Transcriptional Modification - Splicing and other additions mRNA degredation Polypeptide Cleavage / modification / activation Active protein Breakdown of protein Brokendown protein ure 11.9 Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Post-Translational Modification -Cleavage, addition of functional groups 11.4 DNA packing in eukaryotic chromosomes helps regulate gene expression Wound around clusters of histone proteins, forming a string of beadlike nucleosomes Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.6 Complex assemblies of proteins control eukaryotic transcription Proteins involved in Transcription Control: Transcription Factors – act at site of the promoter Activators – bind to the enhancer region of DNA Enhancers Promoter Gene DNA Activator proteins Transcription factors Other proteins RNA polymerase Bending of DNA Figure 11.6 Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Transcription 11.7 Eukaryotic RNA may be spliced in more than one way • After transcription, alternative splicing – May generate two or more types of mRNA from the same transcript Exons DNA RNA transcript or RNA splicing Figure 11.7 mRNA Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings RNAi – RNA Interference Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.8 Translation and later stages of gene expression are also subject to regulation • Once in the Cytoplasm: – mRNA breakdown – Post-translational modification by cleavage, or addition of functional groups like phosphate Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Protein Activation – Polypeptides may require alteration to become functional Folding of polypeptide and formation of S—S linkages Cleavage S S Initial polypeptide (inactive) Folded polypeptide (inactive) Figure 11.8 Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings S S Active form of insulin Protein Breakdown • Some of the proteins that trigger metabolic changes in cells – Are broken down within a few minutes or hours Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.9 Review: Multiple mechanisms regulate gene expression in eukaryotes NUCLEUS Chromosome DNA unpacking Other changes to DNA Gene Gene Transcription Exon RNA transcript Intron Addition of cap and tail Tail Splicing mRNA in nucleus Cap Flow through nuclear envelope mRNA in cytoplasm CYTOPLASM Breakdown of mRNA Translation Brokendown mRNA Polypeptide Cleavage / modification / activation Active protein Breakdown of protein Figure 11.9 Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Brokendown protein