Environment, Epigenome, and Public Health Zhibin Wang Laboratory of Human Environmental Epigenomes Johns Hopkins University What is epigene@cs or epigenomics ? •  Epigene'cs: Heritable changes of gene expression but not due to the changes of DNA sequence •  Epigenome: “-­‐omic” representa@on of all epigene@c phenomena across the genome What are epigene@c mechanisms involved in? •  Major layers of Epigene'c mechanisms: -­‐-­‐-­‐ Histone modifica@on Gene transcrip'on, -­‐-­‐-­‐ Posi@oning of nucleosomes Genomic imprin'ng, Genome stability, and histone variants X-­‐chromosome inac'va'on -­‐-­‐-­‐ DNA methyla@on me ac me me Why is epigenomics or epigene@cs? •  Epigene@cs: connec@ng environment and genotype to phenotype and disease Epigene'cs me ac me Asthma COPD Lung cancer Skin cancer Liver cancer me What do we (epigenomicists) do? me ac me me me ChIP-­‐seq Nu-­‐seq Cell, 2007 Nature Gene,cs, 2008 Immunity, 2009 BMC Genomics, 2009 Cell, 2009 PNAS, 2009 Science, 2010 Nature, 2010 Cur Envion Health Rpt, 2014 EMBO Report, 2014 Cell, 2008 BS-­‐seq or mDIP-­‐seq Nature, 2011 G&D, 2011 Prog Mol Bio Biochem, 2014 Genome Biology (revision) Note, our publica'ons What biology/problems are we interested in? me Biology Fundamental processes ac me Histone modifying complex: Closing chroma@n aWer elonga@on by deacetyl, demethyl, reposi@oning of nucleosome -­‐-­‐endometrial cancer, stomach cancer, colon cancer; inflamma'on; differen'a'on me me DNA methyla'on On genome stability gene transcrip@on genomic imprin@ng 20 novel DMRs in associa@on with 27 common disease -­‐-­‐Early origins of adult disease -­‐-­‐Transgenera'onal epigene'c inheritance -­‐-­‐Environment on sperm fer'lity