| 中文摘要 | 第7-10页 |
| Abstract | 第10-12页 |
| Abbreviations | 第13-14页 |
| Chapter Ⅰ A Brief Review DNA Methylation in Mammalian Development and Progress in Epigenetic Editing | 第14-66页 |
| 1.1 The establishment and maintenance of DNA methylation patterns | 第15-18页 |
| 1.1.1 De novo DNA methylation | 第15-17页 |
| 1.1.2 Maintenance of DNA methylation patterns | 第17-18页 |
| 1.2 Regulation of gene expression by DNA methylation | 第18-20页 |
| 1.2.1 Interaction with transcription factors | 第18-19页 |
| 1.2.2 Recruitment of Methyl-CpG binding proteins and repressor complexes | 第19-20页 |
| 1.3 DNA demethylation | 第20-23页 |
| 1.3.1 Passive DNA methylation | 第20-21页 |
| 1.3.2 Mechanisms of Active DNA methylation | 第21-23页 |
| 1.4 DNA methylation and demethylation in germ cell | 第23-25页 |
| 1.4.1 Germ cell specification and global demethylation | 第23-25页 |
| 1.4.2 Remethylation of germ cell | 第25页 |
| 1.5 DNA methylation and demethylation in mouse early embryos | 第25-28页 |
| 1.6 DNA methylation and genetic imprinting | 第28-36页 |
| 1.6.1 Mammalian Genetic imprinting | 第28-29页 |
| 1.6.2 The role of DNA methylation in genomic imprinting | 第29-32页 |
| 1.6.3 Genetic imprinting and human disease | 第32-36页 |
| 1.7 Genome-wide DNA methylation analysis using next-generation sequencing | 第36-39页 |
| 1.7.1 MeDIP and MethylCap-seq | 第36-37页 |
| 1.7.2 RRBS | 第37-38页 |
| 1.7.3 MethylC-seq | 第38-39页 |
| 1.8. Epigenome Editing: Targeting rewrite epigenetic modifications | 第39-46页 |
| 1.8.1 Targeting DNA demethylation | 第40页 |
| 1.8.2 CRISPR-Cas9 | 第40-43页 |
| 1.8.3 Genome editing using CRISPR-Cas9 in eukaryotic cell | 第43-44页 |
| 1.8.4 Application of CRISPR-Cas9 beyond genome editing | 第44-46页 |
| References | 第46-66页 |
| Chapter Ⅱ Programming and Inheritance of Parental DNA Methylomes in Mammals | 第66-100页 |
| 2.2 Introduction | 第68-70页 |
| 2.3 Method | 第70-76页 |
| 2.4 Results | 第76-91页 |
| 2.4.1 Base-resolution DNA methylome for gametes and early embryos | 第76-78页 |
| 2.4.2 Allele-Specific Dynamics of CpG Methylation during Early Embryogenesis | 第78-80页 |
| 2.4.3 Both paternal and maternal DNA demethylation associated with 5hmC | 第80-85页 |
| 2.4.4 non-CG methylation is passively diluted and positively associated with gene expression | 第85-87页 |
| 2.4.5 Classify imprinting control regions (ICRs) into germ-line ICR and somatic ICR | 第87-89页 |
| 2.4.6 Dynamics of ICR during early embryogenesis | 第89页 |
| 2.4.7 Expression of imprinted genes in ICM | 第89-91页 |
| 2.5 Discussion | 第91-94页 |
| References | 第94-100页 |
| Chapter Ⅲ Develop site-specific epigenome editing approaches based on CRISPR/Cas9 system | 第100-152页 |
| 3.2 Introduction | 第101-105页 |
| 3.3 Materials and Methods | 第105-115页 |
| 3.4 Results | 第115-123页 |
| 3.4.1 Site specific DNA demethylation induced by dCas9 directly binding | 第115-117页 |
| 3.4.2 In vivo study the influence of DNA methylation on protein-DNA interaction | 第117-119页 |
| 3.4.3 dCas9 can efficiently binding to facultative heterochromatin region | 第119-120页 |
| 3.4.4 Site-specific DNA demethylation in H19 ICR mediated by dCas9 | 第120-121页 |
| 3.4.5 Site-specific erasure H3K9 methylation in the heterochromatin | 第121-123页 |
| 3.5 Summary | 第123-124页 |
| 3.6 Discussion | 第124-126页 |
| 3.6.1 Site specific DNA demethylation | 第124页 |
| 3.6.2 DNA demethylation in the ICR mediated by dcas9 | 第124-125页 |
| 3.6.3 CRISPR/Cas9 mediated site specific chromatin modification | 第125页 |
| 3.6.4 Off-target | 第125-126页 |
| References | 第126-152页 |
| 致谢 | 第152-153页 |
| Original Publication | 第153-155页 |
