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Dna methylation
1. DNA METHYLATION Guided by: Presented by: SUSHMA MARLA M.PHARM (First Sem) DEPT. OF BIOTECH. PROF. KALPANA JOSHI PROF. & HEAD BIOTECH. DEPT. SCOE. PUNE.
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12. PRE-IMPLANTATION Genome undergoes Demethylation AFTER IMPLANTATION OF EMBRYO AND DURING CARCINOGENESIS New Methylation patterns are set by de-novo methylation. DURING REPLICATION Methylation patterns must be maintained. Therefore, DNMT1, methylates the hemimethylated DNA after strand synthesis.
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15. CpG ISLANDS PROMOTER REGIONS NON-PROMOTER REGIONS Non-methylated Methylated Binding of TF Transcription Inhibition of TF binding Transcriptional silencing Methylated Non-methylated Silence parasitic genetic elements Genomic stability Binding of TF Transcription
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20. METHYLATION IMBALANCE may contribute to TUMOR PROGRESSION GLOBAL HYPOMETHYLATION DNA HYPERMETHYLATION Observed in neoplastic cells May induce neoplastic transformation Genomic instability, Abnormal chromosomal structures and Activating oncogenes. Inactivation of tumor-suppressor genes: p16, BRCA1 Inactivation of DNA repair genes: MLH1, MGMT
21. A CpG island hypermethylation profile of human cancer
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27. Major Advance: Conversion of unmethylated cystosines to uracil using sodium bisulfite Sequencing: unemethylated cytosines read as thymidine in sense strand; adenine in the anti-sense strand. Other technologies evolved from here.
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