Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis

Clin Immunol. 2013 Oct;149(1):46-54. doi: 10.1016/j.clim.2013.06.006. Epub 2013 Jun 20.

Abstract

Objectives: To investigate alterations in histone modifications in B cells and their role in the pathogenesis of systemic sclerosis (SSc).

Methods: Global histone H3/H4 acetylation and H3K4/H3K9 methylation in B cells of SSc were tested by EpiQuik™ assay kits. Related histone modifier enzymes were measured by RT-PCR and Western blot.

Results: Global histone H4 hyperacetylation and global histone H3K9 hypomethylation were observed in SSc B cells compared with controls. Expression of JHDM2A was significantly increased but HDAC2, HDAC7, and, SUV39H2 were significantly down-regulated in SSc B cells relative to controls. Global histone H4 acetylation and the expression of HDAC2 were negatively correlated. Global histone H3K9 methylation and the expression of SUV39H2 protein were positively correlated. Global H4 acetylation was positively correlated with disease activity and expression of HDAC2 protein was negatively correlated with skin thickness.

Conclusions: Histone modifications were altered in B cells in SSc correlating with skin thickness and disease activity.

Keywords: Acetylation; B cells; Histone modification; Methylation; Systemic sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adult
  • B-Lymphocytes / metabolism*
  • Female
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase 2 / metabolism
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Male
  • Methylation
  • Middle Aged
  • RNA, Messenger / metabolism
  • Scleroderma, Systemic / metabolism*
  • Scleroderma, Systemic / pathology

Substances

  • Histones
  • RNA, Messenger
  • Jumonji Domain-Containing Histone Demethylases
  • Histone-Lysine N-Methyltransferase
  • SUV39H2 protein, human
  • HDAC2 protein, human
  • HDAC7 protein, human
  • Histone Deacetylase 2
  • Histone Deacetylases