The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE.
Despoina Kosmara, Sofia Papanikolaou, Chrysoula Stathopoulou, Dionysios Papamatheakis, Giannis Vatsellas, Arianna Cimmarrusti, Aggelos Banos, Prodromos Sidiropoulos, Matthieu D Lavigne, Panayotis Verginis, Dimitrios Boumpas, Charalampos Spilianakis, Dimitris Konstantopoulos, Christoforos Nikolaou, George Bertsias
Abstract
Open AccessA strong female bias is characteristic of systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease. Here, through an unbiased transcriptome analysis, we report a pronounced female-biased expression of the cohesin complex subunit SMC1A, a genome architectural factor, in monocytes from SLE patients compared to those from healthy individuals or patients with ankylosing spondylitis, a non-sex-biased autoimmune disorder. Integration of SMC1A binding, chromatin activity, and accessibility in lupus-like monocytes reveals extensive SMC1A redistribution to active enhancers of immune/inflammatory genes, inducing their transcription. SLE monocyte transcriptomes demonstrate significant enrichment of female-biased immune/inflammatory genes among SMC1A targets, accompanied by increased secretion of cytokines including IL6, with enhanced SMC1A binding at their enhancers in lupus-like monocytes. Collectively, our study highlights SMC1A as a female-biased chromatin modifier that acquires a specific regulatory function during lupus, accentuating inflammatory pathways and providing mechanistic insights into the female-biased predisposition to SLE and other autoimmune diseases.