Metilazione del DNA Nei vertebrati la metilazione interessa solamente la Citosina: l’enzima citosina metiltransferasi aggiunge un gruppo metile al C5 della citosina: il risulatato è la 5-metilcitosina.
Metilazione nello sviluppo dei mammiferi Demetilazione passiva
Riprogrammazione epigenetica durante la gametogenesi
Fasi di metilazione: Metilazione differenziale de novo (Dnmt3a e Dnmt3b); Demetilazione; Mantenimento della metilazione e trasmissione alle cellule figlie (Dnmt1).
Pathways Representative hypermethylated genes DNA repair hMLH1, MGMT, WRN, BRCA1 Hormone response Estrogen, progesterone, androgen, prolactin and thyroid-stimulating hormone receptors Vitamin response RARB2, CRBP1, Ras signaling RASSFIA, NOREIA Cell cycle p16INK4a, p15INK4b, Rb P53 network p14ARF, p73, HIC-1 Cell adherence and invasion E-cadherin, H-cadherin, FAT cadherin, EXT-1, SLIT2, EMP3 Apoptosis TMS1, DAPK1, WIF-1, SFRP1 Wnt signaling APC, DKK-1, IGFBP-3 Tyrosine kinase cascades SOCS-1, SOCS-3, SYK Transcription factors GATA-4, GATA-5, ID4 Homeobox genes PAX6, HOXA9 Other pathways GSTP1, LKB1/STK11, THBS-14, COX-2, SRBC, RIZ1, TPEF/HPP1, SLC5A8, Lamin A/C microRNAs miR-127 (targeting BCL6), miR-124a (targeting
Laird et al. Epigenomics 5, 655-669
Laird et al. Epigenomics 5, 655-669
Kohli and Zhanget Nature 502, 472-79
Kohli and Zhanget Nature 502, 472-79
Kohli and Zhanget Nature 502, 472-79
Laird et al. Epigenomics 5, 655-669
▪ Cancer-associated hydroxymethylcytosine patterns ▪ General loss of 5hmC ▪ Cancer-specific redistribution with enrichment, particularly at oncogenic gene activators ▪ Possible mechanisms for 5hmC changes in cancer ▪ Replication-related passive demethylation and loss of hydroxymethylcytosine ▪ Misexpression or mutation of TET enzymes, which are responsible for the oxidative conversion of 5mC to 5hmC ▪ Inhibition of the essential TET cofactor, α-ketoglutarate, through mutation of isocitrate dehydrogenase or other Krebs cycle enzymes, such as fumerate hydratase or succinate dehydrogenase Laird et al. Epigenomics 5, 655-669
Laird et al. Epigenomics 5, 655-669