Functional methylome analysis of human diabetic kidney disease

• DOI: 10.1172/jci.insight.128886
• Publication Date: 2019-06-05T15:01:16Z
• Authors: Jihwan Park; Yuting Guan; Xin Sheng; Caroline Gluck; Matthew J. Seasock; Ari Hakimi; Chengxiang Qiu; James Pullman; Amit Verma; Hongzhe Li; Matthew Palmer; Katalin Susztak
• Keywords: 0301 basic medicine; Whole Genome Sequencing; Tumor Necrosis Factor-alpha; DNA Methylation; Kidney; Diabetes Mellitus, Experimental; Epigenome; Mice; 03 medical and health sciences; Animals; Humans; Diabetic Nephropathies; Transcriptome

In patients with diabetes mellitus, poor metabolic control has a long-lasting impact on kidney disease development. Epigenetic changes, including cytosine methylation, have been proposed as potential mediators of the effect adverse events. Our understanding presence and contribution methylation changes to development is limited because lack comprehensive base-resolution methylome information human tissue samples site-specific editing. Base resolution, whole-genome bisulfite sequencing maps diabetic (DKD) tubule samples, associated gene expression measured by RNA highlighted widespread in DKD. Pathway analysis coordinated (methylation expression) immune signaling, tumor necrosis factor alpha (TNF). Changes TNF correlated function decline. dCas9-Tet1–based lowering level differentially methylated region resulted an increase transcript level, indicating that this locus plays important role controlling expression. Increasing mice increased severity, such albuminuria. summary, our results indicate differences DKD kidneys highlights epigenetic its nephropathy mellitus.