Chapter_19_Eukaryotic gene regulation_trimmed.pptx

Biological Science Seventh Edition Chapter 19 Control of Gene Expression in Eukaryotes Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Chapter 19 Opening Roadmap Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Introduction to Control of Gene Expressi...

Biological Science Seventh Edition Chapter 19 Control of Gene Expression in Eukaryotes Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Chapter 19 Opening Roadmap Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Introduction to Control of Gene Expression in Eukaryotes Regulation of gene expression is more complex in eukaryotes than in prokaryotes: – In addition to survival/response to environment, multicellular organisms must establish different cell types Differential gene expression: – Responsible for forming specialized cell types – Arranging them into tissues – Coordinating their activity – Form multicellular society we call an individual Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved In a given cell in a multicellular organism, a lot of the genes will be silent. The cell-type specific genes are activated by a small set of regulatory factors. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 19.1 Gene Regulation in Eukaryotes—An Overview (1 of 3) Eukaryotes can control gene expression at levels of: – Transcription – Translation – Post-translation Additional levels of control- not present in prokaryotes: – Chromatin remodeling – RNA processing – mRNA stability Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Figure 19.1 In Eukaryotes, Gene Expression Can Be Controlled at Many Different Levels Terminology can be a bit confusing: Chromatin remodeling – next few slides Transcriptional Control = step 2 Post-transcriptional control: steps 3 and 4, including alternative splicing Translational control: step 5 Post-translational control: step 6 Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 19.2 Chromatin Remodeling – Chromatin around the target gene must be remodeled: ▪ DNA is packed tightly in nucleus, so tightly that RNA polymerase cannot access it Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Chromatin Structure (1 of 2) Chromatin consists of DNA complexed with histones and other proteins: – Histones—most abundant DNA-associated proteins – Nucleosome—About 200 bases of negatively charged DNA wrap around core of 8 positively charged histone proteins: ▪ Repeating, beadlike structures spaced with linker DNA Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved A given interphase chromosome will have: Some regions permanently inactivated heterochromatin Most of the rest condensed or inaccessible Some available for gene expression - euchromatin Euchromatin means, in effect, that the DNA is loose enough for RNA polymerase to recognize the promoter © 2017 Pearson Education, Inc. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Research: Helper T Cell differentiation Helper T cells are part of the immune system, with Th1 cells helping attack infected cells (cellular response) and Th2 cells helping boost antibody production (humoral response). To do these jobs, the two cell types need to produce different cytokines (secreted signals). For each cell type, some promoters are open and others are permanently not available through chromatin modifications. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 19.3 Initiating Transcription Eukaryotic promoters are more complex than bacterial promoters Have two or three regulatory sequences: – Binding sites for proteins that control gene expression RNA polymerase binds at core promoter: – The most common sequence is the TATA box – A general transcription factor, TBP binds here to help RNA polymerase start transcription Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Promoter-Proximal Elements Are Regulatory Sequences near the Core Promoter Regulatory sequences: – DNA sequences that allow binding of proteins for transcription initiation In eukaryotes: – Co-regulated genes will have the same regulatory DNA sequence – Binds the same type of regulatory protein – Example: steroid response element (SRE)= 5' AGAACAnnnTGTTCT 3' Promoter-proximal elements: – Regulatory sequences close to promoter that are unique to specific sets of genes Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Enhancers Are Regulatory Sequences Far from the Core Promoter (1 of 3) All eukaryotes have enhancers: – Regulatory sequences required for high transcription – Can be more than 100,000 bases away from promoter – There are many types of enhancers – Many genes have more than one enhancer – Enhancers can bind more than one type of regulatory protein. – The DNA sequences work even if their orientation is flipped or they are moved to a new location – Activator (= protein) binds an enhancer; repressor (= protein) binds silencer. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Figure 19.7 Enhancers and PromoterProximal Elements Regulate the Expression of Eukaryotic Genes Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved A Model for Transcription Initiation (1 of 2) Transcription factors must interact with regulatory sequences to initiate transcription General transcription factors: – Interact with core promoter – Not restricted to particular cell types – Do not regulate gene expression – Are required for transcription – Are thought to be among the last to arrive at the gene (see next slides) Mediator—large complex of proteins: – Acts as bridge between regulatory and general transcription factors and RNA Polymerase Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved A Model for Transcription Initiation (2 of 2) One model for transcription initiation in eukaryotes: – Step 0: Default state for a gene is to be buried in heterochromatin, i.e. turned “off.” – Step 1: Regulatory proteins bind to heterochromatin region containing the gene – Step 2: Chromatin remodeling opens chromatin, exposing core promoter and regulatory sequences – Step 3: Other regulatory proteins bind enhancers and promoter-proximal elements; the DNA loops, so mediator and activators interact (see next slide) – Step 4: General transcription factors and R NA polymerase associate with core promoter so that transcription can begin Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Figure 19.9 Transcription Initiation in Eukaryotes Is a Multistep Process Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved New level of gene expression control: Many primary transcripts are alternatively spliced Introns are spliced out of primary RNA transcripts while still in nucleus Alternative splicing: – Leads to production of different mature mRNAs from the same primary transcript – Introns can be retained and exons can be skipped Example: Tropomyosin gene has 14 exons: – Different proteins are produced in different cell types due to alternative splicing. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Figure 19.10 Alternative Splicing Produces More Than One Mature mRNA from the Same Gene Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved mRNA stability is an important mechanism of eukaryotic posttranscriptional control mRNA is produced and exported to cytoplasm: – Other levels of gene expression come into play – Particular mRNAs can be regulated by set of small RNAs Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved RNA Interference Controls the Expression of RNAs (1 of 2) RNA interference (RNAi) controls life span of many mRNAs: – Tiny, single-stranded RNA held by protein complex – Binds to complementary sequence in mRNA – Causes destruction of mRNA or blocks its translation Several types of RNAi: – microRNA (regulation of endogenous mRNAs) – Short interfering RNAs (siRNAs) – PIWI-interacting RN As2014(p iRNEducation, As) Inc. All Rights Reserved Copyright © 2020, 2017, Pearson All siRNAs form RNA duplexes (double-stranded RNA) Details of production are different Small RNAs, bound by a protein complex, recognize complementary sequences on a mRNA End result is interference-- no translation Same effect can be exploited by researchers with artificial siRNAs Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 19.6 A Comparison of Gene Expression in Bacteria and Eukaryotes (1 of 2) Four primary differences between gene expression in bacteria and eukaryotes: 1. ​DNA Packaging—Chromatin structure provides a mechanism of negative control in eukaryotes 2. ​Complexity of transcription—Initiation of transcription is much more complex in eukaryotes 3. ​Coordinated transcription—Bacterial genes may be organized into operons; in eukaryotes a set of regulatory proteins can control many target genes. 4. ​Reliance on post-transcriptional control is much greater in eukaryotes Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Summary: Control of Eukaryotic Gene Expression. Terminology can be a bit confusing: Chromatin remodeling (step 1) Transcriptional Control = step 2 Post-transcriptional control: steps 3 and 4, including alternative splicing Translational control: step 5 Post-translational control: step 6 Copyright © 2020, 2017, 2014 Pearson Education, Inc. 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