The genes in the filtered gene set (FGS) exhibit a lower methylation and a more dynamic pattern across the length of the gene than the rejected genes. apparently identical by descent in B73 and Mo17 suggesting that they may be examples of real epigenetic variance. The methylation levels of the DMRs were further studied in a panel of near-isogenic lines to evaluate the stable inheritance of the methylation levels and to assess the contribution ofcis- andtrans- acting information to natural epigenetic variance. The majority of DMRs that occur AMG 548 in genomic regions without genetic variance are controlled bycis-acting differences and exhibit relatively stable inheritance. This study provides evidence for naturally occurring epigenetic variance in maize, including examples of real epigenetic variance that is not conditioned by genetic differences. The epigenetic differences are variable within maize populations and exhibit relatively stable trans-generational inheritance. The detected examples of epigenetic variance, including some without tightly linked genetic variance, may contribute to complex trait variance. == Author Summary == Heritable variance within a species provides the basis for natural and artificial selection. A substantial portion of heritable variance is based on alterations in DNA sequence among individuals and is termed genetic variance. There is also evidence for epigenetic variance, which refers AMG 548 to heritable differences that are not caused by DNA sequence changes. Methylation of cytosine residues provides one molecular mechanism for epigenetic variance in many eukaryotic species. The genome-wide distribution of DNA methylation was assessed in two different inbred genotypes of maize to identify differentially methylated regions that may contribute to epigenetic variance. There are hundreds of genomic regions that have differences in DNA methylation levels in these two different genotypes, including methylation differences in regions without genetic variance. By studying the inheritance of the differential methylation in near-isogenic progeny of the two inbred lines, it is possible to demonstrate relatively stable inheritance of epigenetic variance, even in the absence of DNA sequence changes. The epigenetic variance among individuals of the AMG 548 same species may provide AMG 548 important contributions to phenotypic variance within a species even in the absence of genetic differences. == Introduction == Much of the heritable variance within a species is a consequence of differences in the primary DNA sequence of different individuals. However, there is growing evidence for heritable variance in the absence of DNA sequence polymorphisms, termed epigenetic variance[1]. Cytosine methylation is one of the molecular mechanisms that can contribute to epigenetic variance and often acts to suppress the activity of GAS1 transposable elements, repetitive sequences, pseudogenes, and in some cases otherwise active genes[2],[3]. There is evidence that epigenetic changes can lead to stable phenotypic variance in grow and animal species[4][10]. However, the large quantity and role of epigenetic, relative to genetic, variance has not been well characterized. Maize (Zea mays) provides a useful model to study the role of epigenetic variance. Genetically, maize is usually a highly diverse species[11],[12]with a large, complex genome with many interspersed genic and repetitive regions[13],[14]. While in the past this complex genomic structure has complicated the ability to perform genome-wide analyses it also is likely to contribute to higher levels of epigenetic variance relative to less complex genomes such as Arabidopsis[3],[15]. In addition, there are outstanding resources for the analysis of quantitative trait variance in maize[16],[17]that may allow for a better understanding of the relative roles of genetic and epigenetic variance in controlling quantitative trait variance. In plants, the majority of genome-wide methylation studies have AMG 548 been conducted in Arabidopsis[18][20],[8]. In these studies DNA methylation was frequently associated with heterochromatic regions, transposable elements, and repetitive DNA[18]. In general, lower levels of methylation occur within gene promoter sequences; however when present, promoter methylation shows a negative correlation with gene expression[19]. Within gene body, regions of DNA methylation have been observed uniquely in the CG context, but no major impact on gene expression is associated with this modification[20]. The exact role of gene body methylation is usually unclear, but it may preferentially impact moderately-transcribed genes[19], and be under different regulatory control than that of transposable element methylation[21]. Similar genome-wide patterns of DNA methylation have also been observed in rice and poplar[22]. A recent analysis of DNA methylation in maize used a 0.3 protection sequencing of McrBC digested DNA to show evidence for mutually unique patterns of DNA methylation and H3K27me3 near genes with low, or no expression[23]. DNA methylation has been proposed to play a role in generating variance that could provide adaptation to environmental stresses[5],[24][27]. Two groups have recently developed epiRIL populations in which epigenetic.