Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Cell nucleus wikipedia , lookup
Protein moonlighting wikipedia , lookup
Histone acetylation and deacetylation wikipedia , lookup
List of types of proteins wikipedia , lookup
Gene regulatory network wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Epitranscriptome wikipedia , lookup
Gene expression wikipedia , lookup
Transcriptional regulation wikipedia , lookup
Chapter 18: Control of Gene Expression 海洋生物研究所 曾令銘 海事大樓 426室 分機: 5326 © 2014 Pearson Education, Inc. Differential Expression of Genes Prokaryotes and eukaryotes precisely regulate gene expression in response to environmental conditions In multicellular eukaryotes, gene expression regulates development and is responsible for differences in cell types RNA molecules play many roles in regulating gene expression in eukaryotes © 2014 Pearson Education, Inc. Concept 18.1: 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 (回饋抑制) or by gene regulation One mechanism for control of gene expression in bacteria is the operon (操縱組) model © 2014 Pearson Education, Inc. Figure 18.2 Precursor Feedback inhibition trpE Enzyme 1 trpD Regulation of gene expression Enzyme 2 trpC trpB Enzyme 3 trpA Tryptophan (a) Regulation of enzyme activity © 2014 Pearson Education, Inc. (b) Regulation of enzyme production Operons: The Basic Concept A cluster of functionally related genes can be coordinately controlled by a single “on-off switch” The “switch” is a segment of DNA called an operator (操作子) usually positioned within the promoter An operon (操縱組) is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control © 2014 Pearson Education, Inc. The operon can be switched off by a protein repressor (抑制物) The repressor prevents gene transcription by binding to the operator and blocking RNA polymerase The repressor is the product of a separate regulatory gene © 2014 Pearson Education, Inc. Figure 18.3a trp operon DNA Promoter Promoter Regulatory gene Genes of operon trpE trpR mRNA 3′ RNA polymerase Operator Start codon trpD trpC trpB trpA Stop codon mRNA 5′ 5′ Protein Inactive repressor E D C B Polypeptide subunits that make up enzymes for tryptophan synthesis (a) Tryptophan absent, repressor inactive, operon on © 2014 Pearson Education, Inc. A The repressor can be in an active or inactive form, depending on the presence of other molecules A corepressor (輔抑制物) is a molecule that cooperates with a repressor protein to switch an operon off For example, E. coli can synthesize the amino acid tryptophan when it has insufficient tryptophan © 2014 Pearson Education, Inc. Figure 18.2 Precursor Feedback inhibition trpE Enzyme 1 trpD Regulation of gene expression Enzyme 2 trpC trpB Enzyme 3 trpA Tryptophan (a) Regulation of enzyme activity © 2014 Pearson Education, Inc. (b) Regulation of enzyme production Figure 18.3b DNA trpR mRNA 5′ trpE No RNA made 3′ Active repressor Protein Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off © 2014 Pearson Education, Inc. By default the trp operon is on and the genes for tryptophan synthesis are transcribed When tryptophan is present, it binds to the trp repressor protein, which turns the operon off The repressor is active only in the presence of its corepressor tryptophan; thus the trp operon is turned off (repressed) if tryptophan levels are high © 2014 Pearson Education, Inc. 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 The trp operon is a repressible operon An inducible operon is one that is usually off; a molecule called an inducer (誘導物) inactivates the repressor and turns on transcription © 2014 Pearson Education, Inc. Figure 18.4a lac operon Regulatory gene Promoter Operator DNA lac I IacZ No RNA made 3′ mRNA 5′ Protein RNA polymerase Active repressor (a) Lactose absent, repressor active, operon off © 2014 Pearson Education, Inc. Figure 18.4b lac operon DNA lac I lacZ RNA polymerase mRNA 3′ Start codon lacY lacA Stop codon mRNA 5′ 5′ Protein β-Galactosidase Inactive repressor Allolactose (inducer) (b) Lactose present, repressor inactive, operon on © 2014 Pearson Education, Inc. Permease Transacetylase The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose By itself, the lac repressor is active and switches the lac operon off A molecule called an inducer (誘導物質) inactivates the repressor to turn the lac operon on © 2014 Pearson Education, Inc. Inducible enzymes usually function in catabolic (分 解代謝的) pathways; their synthesis is induced by a chemical signal Repressible enzymes usually function in anabolic ( 合成代謝的) pathways; their synthesis is repressed by high levels of the end product Regulation of the trp and lac operons involves negative control of genes because operons are switched off by the active form of the repressor © 2014 Pearson Education, Inc. Positive Gene Regulation Some operons are also subject to positive control through a stimulatory protein, such as catabolite activator protein (CAP), an activator of transcription When glucose (a preferred food source of E. coli) is scarce, CAP is activated by binding with cyclic AMP (cAMP) Activated CAP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription © 2014 Pearson Education, Inc. Figure 18.5a Promoter Operator DNA lac I lacZ CAP-binding site cAMP Active CAP Inactive CAP Allolactose RNA polymerase binds and transcribes Inactive lac repressor (a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized © 2014 Pearson Education, Inc. Figure 18.5b Promoter DNA lac I CAP-binding site Inactive CAP lacZ Operator RNA polymerase less likely to bind Inactive lac repressor (b) Lactose present, glucose present (cAMP level low): little lac mRNA synthesized © 2014 Pearson Education, Inc. When glucose levels increase, CAP detaches from the lac operon, and transcription returns to a normal rate CAP helps regulate other operons that encode enzymes used in catabolic pathways © 2014 Pearson Education, Inc. Concept 18.2: Eukaryotic gene expression is regulated at many stages All organisms must regulate which genes are expressed at any given time In multicellular organisms regulation of gene expression is essential for cell specialization © 2014 Pearson Education, Inc. 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 Abnormalities in gene expression can lead to diseases including cancer Gene expression is regulated at many stages © 2014 Pearson Education, Inc. Figure 18.6a Signal Chromatin Chromatin modification: DNA unpacking DNA Gene available for transcription Transcription RNA Exon Primary transcript Intron RNA processing Tail Cap NUCLEUS CYTOPLASM © 2014 Pearson Education, Inc. mRNA in nucleus Transport to cytoplasm Figure 18.6b CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypeptide Protein processing Degradation of protein Active protein Transport to cellular destination Cellular function (such as enzymatic activity or structural support) © 2014 Pearson Education, Inc. Figure 18.UN09 Chromatin modification • Genes in highly compacted chromatin are generally not transcribed. • Histone acetylation seems to loosen chromatin structure, enhancing transcription. • DNA methylation generally reduces transcripton. Transcription • Regulation of transcription initiation: DNA control elements in enhancers bind specific transcription factors. Bending of the DNA enables activators to contact proteins at the promoter, initiating transcription. • Coordinate regulation: Enhancer for liver-specific genes Enhancer for lens-specific genes CHROMATIN MODIFICATION TRANSCRIPTION RNA processing RNA PROCESSING mRNA DEGRADATION TRANSLATION • Alternative RNA splicing: Primary RNA transcript mRNA OR PROTEIN PROCESSING AND DEGRADATION Translation mRNA degradation • Each mRNA has a characteristic life span, determined in part by sequences in the 5′ and 3′ UTRs. © 2014 Pearson Education, Inc. • Initiation of translation can be controlled via regulation of initiation factors. Protein processing and degradation • Protein processing and degradation are subject to regulation.