title: Genomic Clustering of differential DNA methylated regions (epimutations) associated with the epigenetic transgenerational inheritance of disease and phenotypic variation.
abstract: A variety of environmental factors have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation in numerous species. Exposure to environmental factors such as toxicants can promote epigenetic changes (epimutations) involving alterations in DNA methylation to produce specific differential DNA methylation regions (DMRs). The germline (e.g. sperm) transmission of epimutations is associated with epigenetic transgenerational inheritance phenomena. The current study was designed to determine the genomic locations of environmentally induced transgenerational DMRs and assess their potential clustering.
  
  
  
  The exposure specific DMRs (epimutations) from a number of different studies were used. The clustering approach identified areas of the genome that have statistically significant over represented numbers of epimutations. The location of DMR clusters was compared to the gene clusters of differentially expressed genes found in tissues and cells associated with the transgenerational inheritance of disease. Such gene clusters, termed epigenetic control regions (ECRs), have been previously suggested to regulate gene expression in regions spanning up to 2-5 million bases. DMR clusters were often found to associate with inherent gene clusters within the genome.
  
  
  
  The current study used a number of epigenetic datasets from previous studies to identify novel DMR clusters across the genome. Observations suggest these clustered DMR within an ECR may be susceptible to epigenetic reprogramming and dramatically influence genome activity.
authors.affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA.|School of Electrical Engineering and Computer Science, Washington State University, Pullman, WA, 99164, USA.
authors.forename: M Muksitul
authors.initials: MM
authors.lastname: Haque
authors.affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Nilsson
authors.affiliation: School of Electrical Engineering and Computer Science, Washington State University, Pullman, WA, 99164, USA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Holder
authors.affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA. skinner@wsu.edu.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Skinner
mesh_terms: D002874:Chromosome Mapping; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D030541:Databases, Genetic; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D056726:Genetic Association Studies; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype
keywords: Computational Biology; Control Region; DMR; Epigenetics; Review; Transgenerational