NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2

J Cell Mol Med. 2019 Jan;23(1):568-575. doi: 10.1111/jcmm.13961. Epub 2018 Oct 18.

Abstract

Histone lysine methylation plays an important role in the regulation of ventricular remodelling. NSD2 is involved in many types of tumours through enhancing H3K36me2 expression. However, the role of NSD2 in the regulation of histone lysine methylation during ventricular remodelling remains unclear. In this study, we established cardiac hypertrophy model in C57BL/6 mice by transverse aortic constriction and found that histone lysine methylation participated in ventricular remodelling regulation via the up-regulation of H3K27me2 and H3K36me2 expression. In addition, we constructed transgenic C57BL/6 mice with conditional knockout of NSD2 (NSD2-/- ) in the myocardium. NSD2-/- C57BL/6 mice had milder ventricular remodelling and significantly improved cardiac function compared with wild-type mice, and the expression of H3K36me2 but not H3K27me2 was down-regulated. In conclusion, NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2.

Keywords: H3K36me2; NSD2; myocardial infarction; ventricular remodelling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Down-Regulation / genetics
  • Histone-Lysine N-Methyltransferase / genetics*
  • Histones / genetics*
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • Myocardium
  • Up-Regulation / genetics
  • Ventricular Remodeling / genetics*

Substances

  • Histones
  • Histone-Lysine N-Methyltransferase
  • WHSC1 protein, mouse