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

Figure 5

Methylated DNA regions (MRs) of zebrafish gene loci for lig1 (a) and apex1 (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. Those 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) lig1, (b) apex1. The MRs of apex1 are all located within the ORF and are not numbered, although they show a loss of methylation in the DM and/or MM as seen with dnmt1, mcm2, and orc3. In contrast lig1 which did show upregulation in gene expression in the DM and MM states showed the opposite methylation pattern with the control state showing no MRs while the DM and MM states showed the appearance of MRs (Figure 5(a)).

(a)

(b)