Genome-wide DNA methylation map of human neutrophils reveals widespread inter-individual epigenetic variation

The extent of variation in DNA methylation patterns in healthy individuals is not yet well documented. Identification of inter-individual epigenetic variation is important for understanding phenotypic variation and disease susceptibility. Using neutrophils from a cohort of healthy individuals, we generated base-resolution DNA methylation maps to document inter-individual epigenetic variation. We identified 12851 autosomal inter-individual variably methylated fragments (iVMFs). Gene promoters were the least variable, whereas gene body and upstream regions showed higher variation in DNA methylation. The iVMFs were relatively enriched in repetitive elements compared to non-iVMFs, and were associated with genome regulation and chromatin function elements. Further, variably methylated genes were disproportionately associated with regulation of transcription, responsive function and signal transduction pathways. Transcriptome analysis indicates that iVMF methylation at differentially expressed exons has a positive correlation and local effect on the inclusion of that exon in the mRNA transcript

Iron-Catalyzed Olefin Epoxidation and cis-Dihydroxylation by Tetraalkylcyclam Complexes: the Importance of cis-Labile Sites

[Fe(Me2EBC)(OTf)2], the iron(II) complex of the tetraazamacrocyclic Me2EBC ligand (Me2EBC = 4,11-dimethyl-1,4,8,11-tetraazabicyclo [6.6.2]hexadecane), has been investigated as a catalyst for olefin oxidation by H2O2 and compared to the closely related [Fe(TMC)(OTf)](OTf) complex (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). Both complexes have tetraazamacrocyclic ligands based on cyclam that differ in how they coordinate to the iron center. This difference results in different orientations of their remaining coordination sites. Whereas the two sites on [Fe(Me2EBC)(OTf)2] are cis to each other, those of [Fe(TMC)(OTf)](OTf) are trans. Previous work on olefin oxidation by several nonheme iron catalysts has emphasized the importance of having two cis-labile sites to activate the H2O2 oxidant, particularly in effecting olefin cis-dihydroxylation, but there were differences in the ligand donor properties in the complexes studied. The fact that TMC and Me2EBC provide essentially identical tertiary amine donors, but in different orientations, provides an excellent opportunity to assess the impact of ligand topology upon reactivity in the absence of other complicating factors. Indeed [Fe(Me2EBC)(OTf)2] was found to be an active catalyst with reactivity properties similar to those of the most thoroughly investigated iron catalyst [Fe(TPA)(OTf)2] (TPA = tris(pyridin-2-ylmethyl)amine). In contrast, [Fe(TMC)(OTf)](OTf) only showed a limited ability for epoxidation and no facility for cis-dihydroxylation. This stark difference irrefutably demonstrates that cis-oriented labile sites are a fundamental requirement for successful nonheme iron catalyzed olefin oxidation. Additionally, mechanistic studies of [Fe(Me2EBC)(OTf)2] lead us to forward a similar FeIII/FeV redox cycle as proposed for [Fe(TPA)(OTf)2]