3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
| العنوان: | 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus |
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| المؤلفون: | Ming Zhao, Delong Feng, Longyuan Hu, Lin Liu, Jiali Wu, Zhi Hu, Haojun Long, Qiqi Kuang, Lianlian Ouyang, Qianjin Lu |
| المصدر: | Annals of the Rheumatic Diseases. 82:226-234 |
| بيانات النشر: | BMJ, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology |
| الوصف: | ObjectivesThree-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregulated in systemic lupus erythematosus (SLE).MethodsWe performed Hi-C experiments using CD4+T cells from 7 patients with SLE and 5 age-matched and sex-matched healthy controls (HCs) combined with RNA sequencing analysis. Further integrative analyses, including transcription factor motif enrichment, SPI1 knockdown and histone modifications (H3K27ac, H3K4me1, H3K4me3), were performed for altered loop-associated gene loci in SLE.ResultsWe deciphered the 3D chromosome organisation in T cells of patients with SLE and found it was clearly distinct from that of HCs and closely associated with the disease activity of SLE. Importantly, we identified loops within chromosomes associated with the disease activity of SLE and differentially expressed genes and found some key histone modifications close to these loops. Moreover, we demonstrated the contribution of the transcription factor SPI1, whose motif is located in the altered loop in SLE, to the overexpression of interferon pathway gene. In addition, we identified the potential influences of genetic variations in 3D genome alterations in SLE.ConclusionsOur results highlight the 3D genome structure alterations associated with SLE development and provide a foundation for future interrogation of the relationships between chromosome structure and gene expression control in SLE. |
| تدمد: | 1468-2060 0003-4967 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6df6c40ffdcc3924d63c9434a9a700b5 https://doi.org/10.1136/ard-2022-222653 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........6df6c40ffdcc3924d63c9434a9a700b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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