Skip to main content
. Author manuscript; available in PMC: 2020 Oct 1.
Published in final edited form as: Ann Rheum Dis. 2019 Jul 17;78(10):1388–1397. doi: 10.1136/annrheumdis-2019-215567

Figure 5.

Figure 5

A proposed model for the regulatory mechanism of rs2069837 on the expression of GPNMB. The Takayasu arteritis risk allele A at rs2069837 preferentially recruits MEF2 and thereby HDAC proteins compared with the G allele resulting in a repressive effect by weakening the enhancer function at this locus. CTCF binding downstream of this SNP mediates the interaction between this locus and a regulatory locus in GPNMB, where a CTCF binding site also exists. The differential binding of MEF2–HDAC complex between A and G results in differential expression of GPNMB, with inhibited expression in the presence of risk allele A. Inhibiting GPNMB suppresses M2 macrophage polarisation and enhances M1 polarisation and overexpression of proinflammatory cytokines. HDAC, histone deacetylase; MEF2, myocyte enhancer factor 2; SNP, single-nucleotide polymorphism.