Abstract
Background: DNA sequences around HMGB1-produced DNA gaps are hypermethylates. DNA methylation of interspersed repetitive sequences (IRS) such as Alu elements can be established through AGO4-mediating, RNA-directed DNA methylation (RdDM). HMGB1 depletion, DNA gap reductionand global hypomethylation promote genomic instability. Methods: HMGB1, SIRT1, AGO4and DNA gap colocalizations were evaluated. Then, Alu methylationwas analyzed in HMGB1-deficient or HMGB1-overexpressing cells and Alu siRNA-transfected HMGB1-deficient cells. Results: HMGB1, SIRT1, AGO4and DNA gap are colocalized in the nucleus. Moreover, HMGB1 or Alu siRNA increased Alu methylation, whereasAlu siRNA could not methylate HMGB1-deficient cells. Conclusion: AGO4 play a role in methylatingDNA sequence around HMGB1-produced DNA gaps and localize DNA gap in IRS, and loss of intranuclear HMGB1 causes global hypomethylation.
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