| Abstract | 第6-7页 |
| 中文摘要 | 第8-10页 |
| Abbreviations | 第10-15页 |
| Chapter 1 Review of circadian clock | 第15-40页 |
| 1.1 Introduction to circadian clock | 第16-20页 |
| 1.2 Molecular Basis of circadian clock in mammals | 第20-23页 |
| 1.2.1 Molecular components in mammalian circadian clock | 第20-22页 |
| 1.2.2 The transcriptional-translational feedback loop in mammalian circadian clock | 第22-23页 |
| 1.3 Posttranslational modification of circadian clock | 第23-25页 |
| 1.4 Current study of HDAC3 in circadian clock | 第25-26页 |
| 1.5 Entrainment of circadian clock | 第26-28页 |
| References | 第28-40页 |
| Section 1 | 第40-89页 |
| Chapter 2 Genetic depletion of Hdac3 affects circadianrhythms | 第40-57页 |
| Introduction | 第41-42页 |
| Materials and methods | 第42-45页 |
| Results | 第45-52页 |
| 2.1 Genetic depletion of Hdac3 severely reduces the amplitude of circadian rhythms | 第45-48页 |
| 2.2 Genetic depletion of Hdac3 affects circadian gene expression and results in lowBMAL1 and CRY protein levels | 第48-50页 |
| 2.3 HDAC3 promotes BMAL1 enrichment on E-boxes and increases E-boxes drivinggene expression in enzyme independent manner | 第50-52页 |
| Discussion | 第52-53页 |
| References | 第53-57页 |
| Chapter 3 HDAC3 promotes BMAL1 and CRY ubiquitylationin circadian rhythms regulation | 第57-77页 |
| Introduction | 第58-59页 |
| Materials and methods | 第59-61页 |
| Results | 第61-71页 |
| 3.1 HDAC3 associates with BMAL1 and promotes BMAL1 ubiquitylation | 第61-64页 |
| 3.2 HDAC3 Blocks FBXL3-Mediated CRY1 and CRY2 Degradation | 第64-68页 |
| 3.3 HDAC3 Promotes the Assembly of the BMAL1-CRY1 Complex during theRepression Phase | 第68-71页 |
| Discussion | 第71-73页 |
| References | 第73-77页 |
| Chapter 4 The effect of HDAC3 on BMAL1 and CRY1 isindependent of its deacetylase activity and PER2 | 第77-89页 |
| Introduction | 第78页 |
| Materials and methods | 第78-80页 |
| Results | 第80-85页 |
| 4.1 The effect of HDAC3 on BMAL1 and CRY1 is independent of its deacetylase activity | 第80-83页 |
| 4.2 The effect of HDAC3 on BMAL1 and CRY1 is independent of PER2 | 第83-85页 |
| Discussion | 第85-87页 |
| References | 第87-89页 |
| Section 2 | 第89-112页 |
| Chapter 5 High-throughput discovery of genetic determinantsfor circadian entrainment | 第89-102页 |
| Introduction | 第91-92页 |
| Materials and methods | 第92-93页 |
| Results | 第93-97页 |
| 5.1 Developing a screening strategy using IMPC resource | 第93-94页 |
| 5.2 Determine reliable and quantifiable positive biomarkers and genetic determinants forcircadian entrainment | 第94-97页 |
| Discussion | 第97-98页 |
| References | 第98-102页 |
| Chapter 6 The validation of phenotypes and mechanisminsights | 第102-112页 |
| Introduction | 第103页 |
| Materials and methods | 第103-105页 |
| Results | 第105-108页 |
| 6.1 Circadian dependent gene expression in mouse liver and olfactory bulb | 第105-107页 |
| 6.2 Circadian signaling pathway association | 第107-108页 |
| Discussion | 第108-110页 |
| References | 第110-112页 |
| 致谢 | 第112-113页 |
| Publications | 第113-117页 |
