| Abstract | 第1-6页 |
| 摘要 | 第6-8页 |
| Table of Contents | 第8-11页 |
| 1. Introduction | 第11-31页 |
| ·DNA methylation in mammals | 第11页 |
| ·DNA methyltransferases (Dnmts) | 第11-15页 |
| ·Dnmt1 | 第11-13页 |
| ·Dnmt2 | 第13-14页 |
| ·Dnmt3 | 第14-15页 |
| ·Diversification in physical properties of Dnmts | 第15-16页 |
| ·DNA methylation chemistry | 第16页 |
| ·Interaction of Dnmts with other proteins | 第16-18页 |
| ·DNA methylation during early embryogenesis | 第18-19页 |
| ·DNA methylation in embryonic stem cells | 第19-21页 |
| ·DNA methylation during neuronal differentiation | 第21-27页 |
| ·DNA methylation and neurological disorders | 第27-30页 |
| ·Objectives of this study | 第30-31页 |
| 2. Materials and methods | 第31-36页 |
| ·Antibodies | 第31页 |
| ·Cell culture and transfections | 第31页 |
| ·Western blot analysis | 第31-32页 |
| ·Immunocytochemistry | 第32页 |
| ·Real-time quantitative RT-PCR analysis | 第32-33页 |
| ·Chromatin Immunoprecipitation (ChIP) analysis | 第33页 |
| ·Bisulfite genomic sequencing, COBRA, and MSP | 第33-34页 |
| ·Lentiviral shRNA vector production and infection | 第34页 |
| ·Cell cycle and cell proliferation assays | 第34-35页 |
| ·Analysis of cell apoptosis | 第35页 |
| ·Statistical analysis | 第35-36页 |
| 3. Results | 第36-61页 |
| ·Epigenetic regulation of Dpp6 expression by Dnmt3b and its novel role in the inhibition of RA induced neuronal differentiation of P19 cells | 第36-51页 |
| ·RA induced neuronal differentiation of P19 cells using serum-free and monolayer culture | 第36页 |
| ·Differential Expression of DNA methyltransferases during differentiation of P19 cells | 第36-40页 |
| ·Identification of novel targets of Dnmt3b in P19 derived neurons | 第40-41页 |
| ·Association of Dnmt3b with the promoter of Dpp6 gene in P19 cells | 第41页 |
| ·Methylation pattern of Dpp6 promoter CpG Island and its expression in P19 cells | 第41-44页 |
| ·Down-regulation of Dnmt3b resulted in increased expression and decreased methylation of Dpp6 gene | 第44页 |
| ·In the absence of Dnmt3b, Dnmt3a regulated the expression and methylation of Dpp6 gene in P19 cells | 第44-48页 |
| ·Ectopic Dpp6 expression resulted in impaired neuronal differentiation of P19 cells | 第48-51页 |
| ·RA induced transcriptional silencing of Checkpoint Kinase-2 through promoter methylation by Dnmt3b and its role during neuronal differentiation of P19 cells | 第51-61页 |
| ·Recruitment of Dnmt3b on Chk2 promoter is induced by RA treatment | 第51页 |
| ·Methylation level of Chk2 promoter CpG Island is increased after RA treatment of P19 cells | 第51-54页 |
| ·Expression of Chk2 during RA induced neuronal differentiation of P19 cells | 第54-55页 |
| ·Dnmt3b knockdown resulted in increased expression and decreased methylation of Chk2 | 第55-56页 |
| ·Effect of enforced Chk2 expression on neuronal differentiation, cell cycle profile and apoptosis after RA treatment of P19 cells | 第56-61页 |
| 4. Discussion | 第61-66页 |
| ·Expression of Dnmts during RA induced neuronal differentiation of P19 cells | 第61-62页 |
| ·Regulation of Dpp6 expression and its novel role during RA induced neuronal differentiation of P19 cells | 第62-64页 |
| ·Regulation of Chk2 expression and its function in neuronal differentiation of P19 cells | 第64-66页 |
| Conclusions and future prospects | 第66-67页 |
| References | 第67-81页 |
| Acknowledgements | 第81-83页 |
| List of publications (2009—2013) | 第83页 |
