PUBLICATION
Epigenetic Studies Point to DNA Replication/Repair Genes as a Basis for the Heritable Nature of Long Term Complications in Diabetes
- Authors
- Leontovich, A.A., Intine, R.V., Sarras, M.P.
- ID
- ZDB-PUB-160317-6
- Date
- 2016
- Source
- Journal of Diabetes Research 2016: 2860780 (Journal)
- Registered Authors
- Sarras, Michael P., Jr.
- Keywords
- none
- MeSH Terms
-
- Phenotype
- Epigenesis, Genetic*
- Animals
- Diabetes Mellitus, Experimental/blood
- Diabetes Mellitus, Experimental/complications*
- Zebrafish
- DNA Replication/genetics*
- DNA Repair Enzymes/genetics*
- Gene Regulatory Networks
- Heredity*
- DNA Methylation
- Blood Glucose/metabolism
- Energy Metabolism/genetics*
- Genetic Predisposition to Disease
- Disease Models, Animal
- DNA Repair/genetics*
- Oligonucleotide Array Sequence Analysis
- Diabetes Complications/genetics*
- Diabetes Complications/metabolism
- Animal Fins/metabolism
- Computational Biology
- Gene Expression Profiling/methods
- PubMed
- 26981540 Full text @ J. Diabetes Res.
Citation
Leontovich, A.A., Intine, R.V., Sarras, M.P. (2016) Epigenetic Studies Point to DNA Replication/Repair Genes as a Basis for the Heritable Nature of Long Term Complications in Diabetes. Journal of Diabetes Research. 2016:2860780.
Abstract
Metabolic memory (MM) is defined as the persistence of diabetic (DM) complications even after glycemic control is pharmacologically achieved. Using a zebrafish diabetic model that induces a MM state, we previously reported that, in this model, tissue dysfunction was of a heritable nature based on cell proliferation studies in limb tissue and this correlated with epigenetic DNA methylation changes that paralleled alterations in gene expression. In the current study, control, DM, and MM excised fin tissues were further analyzed by MeDIP sequencing and microarray techniques. Bioinformatics analysis of the data found that genes of the DNA replication/DNA metabolism process group (with upregulation of the apex1, mcm2, mcm4, orc3, lig1, and dnmt1 genes) were altered in the DM state and these molecular changes continued into MM. Interestingly, DNA methylation changes could be found as far as 6-13 kb upstream of the transcription start site for these genes suggesting potential higher levels of epigenetic control. In conclusion, DNA methylation changes in members of the DNA replication/repair process group best explain the heritable nature of cell proliferation impairment found in the zebrafish DM/MM model. These results are consistent with human diabetic epigenetic studies and provide one explanation for the persistence of long term tissue complications as seen in diabetes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping