DMMC Course: EPIGENETICS: FROM MECHANISMS TO MEDICINES

1745-1845 Tuesday 26 June 2007. O’Reilly Hall, University College Dublin.

Cancer Epigenomics
Prof Peter Jones (USC / Norris Comprehensive Cancer Center, USA)

Epigenetic silencing of tumor suppressor genes plays a major role in human carcinogenesis. CpG islands can become abnormally methylated resulting in heritable silencing. This methylation of cytosine residues is associated with alterations in chromatin structure including the binding of methylated DNA binding proteins and changes in the state of covalent modification of histone residues in nucleosomes. Cancer cells with epigenetically silenced promoters show not only extensive DNA cytosine methylation and deacetylated histones but also have extra nucleosomes in the promoter. Strikingly activation of the silenced promoters by DNA demethylating drugs involves nucleosomal eviction in addition to changes in cytosine methylation and covalent histone modifications.