Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Distinguishing hyperglycemic changes by Set7 in vascular endothelial cells.

RATIONALE: Epigenetic changes are implicated in the persisting vascular effects of hyperglycemia. The precise mechanism whereby chromatin structure and subsequent gene expression are regulated by glucose in vascular endothelial cells remain to be fully defined. OBJECTIVE: We have studied the molecular and functional mechanism whereby the Set7 methyltransferase associates with chromatin formation and histone methylation in vascular cells in response to current and previous exposure to glucose. METHODS AND RESULTS: To characterize the molecular and functional identity of the Set7 protein, we used vascular cells overexpressing or lacking Set7. Chromatin fractionation for mono-methylation of lysine 4 on histone H3 identified methyltransferase activity. Immunofluorescence experiments strongly suggest that Set7 protein accumulates in the nucleus in response to hyperglycemia. Moreover, activation of proinflammatory genes by high glucose is dependent on Set7 but distinguished by H3K4m1 gene patterns. We show that transient hyperglycemia regulates the expression of proinflammatory genes in vascular endothelial cells in vitro and the persistent increase in glucose-induced gene expression in the aorta of nondiabetic mice. CONCLUSIONS: This study uncovers that the response to hyperglycemia in vascular endothelial cells involves the H3K4 methyltransferase, Set7. This enzyme appears to regulate glucose-induced chromatin changes and gene expression not only by H3K4m1-dependent but also H3K4m1-independent pathways. Furthermore, Set7 appears to be responsible for sustained vascular gene expression in response to prior hyperglycemia and is a potential molecular mechanism for the phenomenon of hyperglycemic memory.

Pubmed ID: 22403242


  • Okabe J
  • Orlowski C
  • Balcerczyk A
  • Tikellis C
  • Thomas MC
  • Cooper ME
  • El-Osta A


Circulation research

Publication Data

April 13, 2012

Associated Grants


Mesh Terms

  • Animals
  • Aorta
  • Cell Line
  • Cell Nucleus
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Diabetic Angiopathies
  • Disease Models, Animal
  • Endothelial Cells
  • Gene Expression Regulation
  • Glucose
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Hyperglycemia
  • Inflammation
  • Inflammation Mediators
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Protein Methyltransferases
  • RNA Interference
  • Time Factors
  • Transfection