The X-linked chromatin modifier SMC1A is deregulated in lupus female monocytes and promotes autoimmunity [ChIP-Seq]

Biological sex underlines the onset of autoimmunity yet the underlying molecular mechanisms remain ill-defined. Female susceptibility is prominent in systemic lupus erythematosus (SLE), an autoimmune disease of substantial burden. Herein we demonstrate that SMC1A, a subunit of the cohesin complex that escapes X-chromosome inactivation, exhibits female-biased expression in monocytes from SLE patients and those cultured under lupus-inducing stimulus. By altering SMC1A dosage, the expression of immune-related genes, particularly those responsive to lupus environment, was affected. Active enhancers of immune and inflammatory pathways showed widespread SMC1A redistribution in lupus-like monocytes, as revealed by integrated analysis of SMC1A binding, chromatin activity and accessibility. Our data support SMC1A as a sex-biased chromatin modifier that enhances inflammatory responses in lupus.