武汉大学生命科学学院：《分子生物学》（英文版）Part IV：Regulation CHAPTER17 Gene Regulation in Eukaryotes

Molecular biology of the Gene 5/E - Watson et al. ( 2004) Part l: chemistry and genetics Part l: Maintenance of the Genome Part l: Expression of the Genome Part Iv: Regulation Part v: Methods 2005-5-10 刻博来字 Wuhan Universit

2 Molecular Biology of the Gene, 5/E --- Watson et al. (2004) Part I: Chemistry and Genetics Part II: Maintenance of the Genome Part III: Expression of the Genome Part IV: Regulation Part V: Methods 2005-5-10

Part IV Regulation Ch16: Requlation in prokaryotes Ch 17: Regulation in eukaryotes Ch 18: Regulation during development and in diseases(brief introduction Ch 19; Comparative genomics and evolution of anima/ diversity(Not covered in the lecture)

3 Part IV Regulation Ch 16: Regulation in prokaryotes Ch 17: Regulation in eukaryotes Ch 18: Regulation during development and in diseases (brief introduction) Ch 19: Comparative genomics and evolution of animal diversity (Not covered in the lecture)

Chapter 16 Regulation principles and How genes are regulated in bacteria Chapter 17 Basic mechanism of gene expression in eukaryotes Chapter 18 The mechanism of rnai and the role of miRNA in development and cancergenesis

4 Chapter 16 Regulation principles and How genes are regulated in bacteria Chapter 17 Basic mechanism of gene expression in eukaryotes Chapter 18 The mechanism of RNAi and the role of miRNA in development and cancergenesis

Surfing the contents of PartA -The heart of the frontier biologica isciplines

5 Surfing the contents of Part IV --The heart of the frontier biological disciplines

Molecular Biology Course Chapter 17 Gene Regulation in Eukaryotes 隅来字 Wuhan University

6 Chapter 17 Gene Regulation in Eukaryotes •Molecular Biology Course

2. 1. Gene Expression is Controlled by 3. Regulatory Proteins(调控蛋白) Gene expression is very often controlled by Extracellular Signals, which are communicated to genes by regulatory proteins: Positive requlators or activators INCREASE the transcription F>Negative regulators or repressors DECREaSE or elIMinate the transcription

7 1. Gene Expression is Controlled by Regulatory Proteins (调控蛋白) Gene expression is very often controlled by Extracellular Signals, which are communicated to genes by regulatory proteins: ➢ Positive regulators or activators INCREASE the transcription ➢ Negative regulators or repressors DECREASE or ELIMINATE the transcription Principles of Transcription Regulation

Similarity of regulation between eukaryotes and prokaryote 1.Principles are the same ignals(信号 activators and repressors(激活蛋白和阻 遏蛋白 recruitment and allostery, cooperative binding(招募,异构和协同结合) 2. The gene expression steps subjected to requlation are similar, and the initiation of transcription is the most pervasively regulated step

8 Similarity of regulation between eukaryotes and prokaryote 1.Principles are the same: • signals (信号), • activators and repressors (激活蛋白和阻 遏蛋白) • recruitment and allostery, cooperative binding (招募，异构和协同结合) 2. The gene expression steps subjected to regulation are similar, and the initiation of transcription is the most pervasively regulated step

Difference in regulation between eukaryotes and prokaryote 1. Pre-mRNA splicing adds an important step for regulation.(mRNA前体的剪接 2. The eukaryotic transcriptional machinery is more elaborate than its bacterial counterpart.(真核转录机器更复杂 Nucleosomes and their modifiers influence access to genes.(核小体及其修饰体 4. Many eukaryotic genes have more regulatory binding sites and are controlled y more regulatory proteins than are bacterial genes.(真核基因有更多结合位点

9 Difference in regulation between eukaryotes and prokaryote 1. Pre-mRNA splicing adds an important step for regulation. (mRNA前体的剪接) 2. The eukaryotic transcriptional machinery is more elaborate than its bacterial counterpart. (真核转录机器更复杂) 3. Nucleosomes and their modifiers influence access to genes. (核小体及其修饰体) 4. Many eukaryotic genes have more regulatory binding sites and are controlled by more regulatory proteins than are bacterial genes. (真核基因有更多结合位点)

A lot more regulator bindings sites in multicellular organisms reflects the more exTensive signal inTegraTion regulatory promoter Bacteria sequence Yeast Human Fig. 17-1

10 A lot more regulator bindings sites in multicellular organisms reflects the more extensive signal integration Fig. 17-1 Bacteria Yeast Human

Enhancer(激活元件): a given site binds regulator responsible for activating the gene. Alternative enhancer binds different groups of regulators and control expression of the same gene at different times and places in responsible to different signals Activation at a distance is much more common in eukaryotes. Insulators(绝缘子) or boundary elements(临界元 f)are regulatory sequences between enhancers and promoters. They block activation of a linked promoter by activator bound at the enhancer and therefore ensure activators work discriminately

11 Enhancer (激活元件) : a given site binds regulator responsible for activating the gene. Alternative enhancer binds different groups of regulators and control expression of the same gene at different times and places in responsible to different signals. Activation at a distance is much more common in eukaryotes. Insulators (绝缘子) or boundary elements (临界元 件) are regulatory sequences between enhancers and promoters. They block activation of a linked promoter by activator bound at the enhancer, and therefore ensure activators work discriminately