CpG islands CpG is under-represented throughout most of genome but is found at expected frequencies in short -1 Kb stretches Enrichment of cpg in these regions led to designation as cpg islands ooo,000 CpG islands in genome, and these are mostly located at promoters within first exons of genes CpG islands are unmethylated in normal cells Methylation of CpGs near tumor suppressor genes (p53 or p16) often related to silencing of these genes in tumors 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 21 CpG Islands: ••• CpG is under-represented throughout most of genome but is found at expected frequencies in short ~1 KB stretches. ••• Enrichment of CpG in these regions led to designation as CpG islands. ••• ~45,000 CpG islands in genome, and these are mostly located at promoters within first exons of genes. ••• CpG islands are unmethylated in normal cells Methylation of CpGs near tumor suppressor genes (p53 or p16) often related to silencing of these genes in tumors
1. DNA methylation Cytosine is methylated by a N several enzymes Cytosine Maintenance of methylation allows the modification to SAMCH NMT become heritable SAM NH Note during replication the 5-Methyicyosine parent strands will be methylated Mechanism of DNA methylatlon In mammals cpg is the site for methylation Methylated promoters are associated with silent genes 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 22 1. DNA methylation Cytosine is methylated by a several enzymes Maintenance of methylation allows the modification to become heritable Note during replication the parent strands will be methylated In mammals CpG is the site for methylation Methylated promoters are associated with silent genes
NH NH CH3 5-Methyl- Cytosine Cytosine Mtase SAMD SA豆 DNA methylation refers to the transfer of a methyl( CH3 group) to one of the bases that constitute dNA. the reaction is catalyzed by a dna methyltransferase( Mtase), and uses s Adenosyl Methionine(SAM) as a methyl donor. In humans, normal dNa methylation is limited to the cytosine base 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 23 DNA methylation refers to the transfer of a methyl (CH3 group) to one of the bases that constitute DNA. The reaction is catalyzed by a DNA methyltransferase (Mtase), and uses SAdenosyl Methionine (SAM) as a methyl donor. In humans, normal DNA methylation is limited to the Cytosine base
CpG islands: >200 bp stretches of dna that have a significantly higher concentration of 5'-CpG 3 dinucleotides than the bulk of the genome Cytosine resudue in complementary 3 -GpC-5 that makes a basepair, is also methylated symmetrically, and these two methyl groups show a three-dimentional structure prominent in the major groove of the dsDNA 50-60% of human genes have cpg islands in front of and covering core promotor and transcription start site 70-80%of CpGs in the genome is methylated 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 24 * CpG islands: >200 bp stretches of DNA that have a significantly higher concentration of 5’-CpG;3’ dinucleotides than the bulk of the genome * Cytosine resudue in complementary 3’-GpC-5’ that makes a basepair, is also methylated symmetrically, and these two methyl groups show a three-dimentional structure prominent in the major groove of the dsDNA * 50-60% of human genes have CpG islands in front of and covering core promotor and transcription start site * 70-80% of CpGs in the genome is methylated
CpG islands in front of genes are mostly unmethylated exceptions: imprinted genes and x-linked genes CpG island are divided into several classes (1)methylated on both alleles in all tissues located in high cg isochores (2)differentially methylated and located in low CG (<0.5)isochores genomic methylation pattern is stable and heritable genome-wide methylation patterns are reprogrammed in mammalian germ cells and in pre-implantation embryos 2005-10-29 Chaoqun Wu, Fudan University
2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 25 * CpG islands in front of genes are mostly unmethylated exceptions: imprinted genes and X-linked genes * CpG island are divided into several classes: (1) methylated on both alleles in all tissues located in high CG isochores (2) differentially methylated and located in low CG (<0.5) isochores *genomic methylation pattern is stable and heritable *genome-wide methylation patterns are reprogrammed in mammalian germ cells and in pre-implantation embryos