Epigenetic Studies Point to DNA Replication/Repair Genes as a Basis for the Heritable Nature of Long Term Complications in Diabetes

Figure 6

Methylated DNA regions (MRs) of zebrafish gene loci for mcm4 (a) and pola2 (b). Panels (a) and (b) were prepared with IGV genome viewer. The scale on the top shows chromosomal coordinates. This program schematically represents the structure of the gene using conventional elements: (1) blue line represents introns and (2) blue blocks on the line represent exons. Circles with the “TSS” point to the transcription start site and the dashed arrow points in the direction of 5′ to 3′ of the DNA strand with the arrow pointing to the MR farthest upstream of the TSS as indicated for each diagram (bp distance indicated in the box above the dashed arrow). Three tracks separated by gray lines below gene track show localization of MRs for each of the three samples to include control (CTRL), diabetic state (DM), and metabolic memory state (MM). Methylated regions detected by the MACS algorithm are shown as red boxes. MRs upstream of the TSS that have a loss of methylation in the DM and/or MM states are numbered (MR1, MR2, etc.) with the MACS peak ID numbers under each MR. (a) mcm4, (b) pola2. As shown in Figure 6(b), pola2 mimicked lig1. Like lig1, pola2 displayed upregulation of gene expression in the DM and MM states but showed no differential methylation pattern in the control state. Also like lig1, pola2 was seen to have MRs detected in the DM and/or MM states.

(a)

(b)