报告人简介：Paul A. Wade, Ph.D., is Acting Deputy Scientific Director, Deputy Chief of the Epigenetics and Stem Cell Biology Laboratory and head of the Eukaryotic Transcriptional Regulation Group, NIEHS, Research Triangle Park, NC, USA. The group is interested in defining gene regulatory mechanisms and identifying key regulatory molecules with a focus on chromatin modification. Currently, the group’s studies center on the Mi-2/NuRD complex, a multi-subunit chromatin modification enzyme (Wade et al., 1998). The complex consists of a SNF2-related chromatin remodeling ATPase (Mi-2), a member of the MBD family of methyl CpG binding domain proteins (MBD3), histone deacetylases (HDAC1 and HDAC2), a histone binding protein (RbAp46/p48), a protein of unknown function (known as p66), and an interesting subunit encoded by one of three genes (MTA1, MTA2, or MTA3) in mammals (Wade et al., 1999).

报告摘要🌗：DNA methylation is an essential epigenetic mark, intimately involved in mammalian gene regulation. The pattern of DNA methylation is dramatically reprogrammed at multiple points between generations in mammals. While local DNA sequence and overall genetic background are known to influence histone modification patterns, the extent to which DNA methylation patterns are impacted by genetics remains incompletely understood. We addressed this issue by intercrossing inbred mouse strains and analyzing DNA methylation at the base-pair level across the genome in somatic tissue from parents and age-matched offspring of multiple families. Loci at which CpG methylation differed between strains were generally located far from transcription start sites, were associated with regulatory DNA elements and offspring had methylation levels intermediate between parental levels. In the vast majority of cases, differential CpG methylation patterns observed in parents were preserved on the relevant parental alleles in offspring. At differentially methylated regions, DNA sequence differences between strains frequently occurred within enriched transcription factor binding sites where deviations from consensus at invariant residues were associated with increases in local DNA methylation. These results support a framework to understand the manner in which genetic differences between inbred strains, or between individuals in outbred populations including humans, impact the epigenetic features that dictate gene expression patterns characteristic of health and disease.