BackgroundDNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells.ResultsExamining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes) and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines.ConclusionsComparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.

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Research Summary Divisions into an “us” and a “them” across racial, ethnic, economic, geographic, and other demographic divides impede society's capacity to address grand challenges. Firms have an impact on such divisions—whether positively or negatively, intentionally or not—through the dual mechanisms of rents and relationships. Firms may contribute to horizontal inequalities that underlie intergroup conflict through the distribution of the benefits, costs, and risks of firm activities. Through their relational strategies, firms also shape the willingness and ability of different groups to work together for positive change. Firm behaviors emerging from their daily operations can thus change society's capacity to address its grand challenges, necessitating corporate activism that encompasses market and nonmarket strategies, as well as a broader understanding of the strategy‐setting process itself. Managerial Summary This paper examines how firms inevitably shape conflict and cooperation in society through their impact on relationships between groups across racial, ethnic, economic, geographic, and other demographic boundaries. Managers distribute the gains and losses of business activities in ways that differently impact identity groups attentive to their relative inequalities. Strategies regarding how stakeholder relationships are built or broken can also change the ability of groups to build consensus on issues of broad social concern. We explain how these managerial decisions can thus affect the capacity of broader society to address collective challenges. We further explore how managers can design and implement inclusive market and nonmarket strategies that strengthen the cooperative potential of different groups to advance important social goals.

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