PartⅢ DNA methylation 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 16 Part III. DNA methylation
Biological phenomena Transcription, Replication, Repair, Recombination Development, Reprogramming, Aging, Tumorigenesis DNA methylation Protein modification Epigenetics Chromatin 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 17
Box 1 The three main types of epigenetic information Cytosine dNa methvlation is a covalent modification of DNA, in which a methyl group is transferred from S-adenosylmethionine to the c-5 position of cytosine by a family of cytosine (DNA-5)-methyltransferases. DNA methylation occurs almost exclusively at CPG nucleotides and has an important contributing role in the regulation of gene expression and the silencing of repeat elements in the genome Genomic imprinting is parent-of-origin-specific allele silencing, or relative silencing of one parental allele compared with the other parental allele It is maintained, in part, by differentially methylated regions within or near imprinted genes, and it is normally reprogrammed in the germline Histone modifications -including acetylation, methylation and phosphorylation-are important in transcriptional regulation and many are stably maintained during cell division although the mechanism for this epigenetic inheritance is not yet well understood. Proteins that mediate these modifications are often associated within the same complexes as those that regulate DNA methylation 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 18
DNA甲基化 ■真核生物的DNA甲基化主要是胞嘧啶的 第5位碳原子上加上甲基,催化这一反 应的为DNA甲基化转移酶(Dnmt) ■真核生物的DNA维持较低水平的甲基 化,且大部分甲基化集中在CpG序列 上 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 19 DNA甲基化 真核生物的DNA甲基化主要是胞嘧啶的 甲基化主要是胞嘧啶的 第5位碳原子上加上甲基，催化这一反 位碳原子上加上甲基，催化这一反 应的为DNA甲基化转移酶（ 甲基化转移酶（Dnmt)。 真核生物的DNA维持较低水平的甲基 维持较低水平的甲基 化，且大部分甲基化集中在 化，且大部分甲基化集中在CpG序列 上
DNA Methylation > Cytosines in palindromic cg dinucleotides are subject to methylation at the carbon 5 position in plants and vertebrates >Methylation does not alter base pairing Cpg methylation does not occur in yeast or Drosophila >70%of cytosines in Cp Gs are methylated in vertebrates > CpG methylation is regulated tightly during development and is associated with gene silencing X-inactivation, and allele-specific imprinting 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 20 DNA Methylation ¾Cytosines in palindromic CG dinucleotides are subject to methylation at the carbon 5 position in plants and vertebrates ¾Methylation does not alter base pairing ¾CpG methylation does not occur in yeast or Drosophila ¾~70% of cytosines in CpGs are methylated in vertebrates ¾CpG methylation is regulated tightly during development and is associated with gene silencing, X-inactivation, and allele-specific imprinting