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

Figure 4

Methylated DNA regions (MRs) of zebrafish gene loci for dnmt1 (a), mcm2 (b), and orc3 (c). Panels (a), (b), and (c) 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 are lost in both the DM and MM states are numbered (MR1, MR2, etc.) and shown within circles over the red bars. The sequence counts for MACS peaks are shown under each MR. (a) dnmt1, (b) mcm2, and (c) orc3. (a) dnmt1, chromosomal coordinates are chr3:53,494,972-53,510,920; (b) mcm2, chromosomal coordinates are chr22:3,992,357-4,013,603; and (c) orc3, chromosomal coordinates are chr17:44,806,126-44,836,951.

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