The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE
A 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.
Authors
- Christoforos Nikolaou (ORCID: https://orcid.org/0000-0003-3001-6786)
- Aggelos Banos (ORCID: https://orcid.org/0000-0002-5647-6505)
- Dimitrios T. Boumpas (ORCID: https://orcid.org/0000-0002-9812-4671)
- George K Bertsias (ORCID: https://orcid.org/0000-0001-5299-1406)
- Panayotis Verginis (ORCID: https://orcid.org/0000-0002-1282-5435)
- Dionysios-Alexandros Papamatheakis (ORCID: https://orcid.org/0000-0002-3107-9335)
- Chrysoula Stathopoulou
- Sofia Papanikolaou (ORCID: https://orcid.org/0000-0003-1945-1322)
- Giannis Vatsellas (ORCID: https://orcid.org/0000-0002-1631-1060)
- Matthieu D. Lavigne (ORCID: https://orcid.org/0000-0003-1543-8745)
- Charalampos G. Spilianakis (ORCID: https://orcid.org/0000-0003-0921-1923)
- Prodromos I. Sidiropoulos (ORCID: https://orcid.org/0000-0001-9607-0326)
- Dimitris Konstantopoulos (ORCID: https://orcid.org/0000-0003-2142-3021)
- Δέσποινα Κοσμαρά (ORCID: https://orcid.org/0009-0006-2289-3833)
- Arianna Cimmarrusti (ORCID: https://orcid.org/0009-0007-7370-4091)
Institutions
- University of Crete (GR)
- Academy of Athens (GR)
- FORTH Institute of Molecular Biology and Biotechnology (GR)
- Institute of Molecular Biology and Biotechnology (BG)
- Alexander Fleming Biomedical Sciences Research Center (GR)
- Foundation for Research and Technology Hellas (GR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s41467-025-65309-7
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- State Scholarships Foundation
- Hellenic Foundation for Research and Innovation
- European Social Fund