Integrated analysis of ATAC-seq and RNA-seq reveals the chromatin accessibility and transcriptional landscape of immunoglobulin a nephropathy.

Clin Immunol

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Center for Big Data and Population Health of IHM, Hefei, Anhui, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, 81 Meishan Road, Hefei, Anhui, China. Electronic address:

Published: January 2025

Backgrounds: The association between chromatin accessibility in CD4 T cells and Immunoglobulin A nephropathy (IgAN) remains unclear.

Methods: We performed the assay for transposase accessible chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq) on CD4 T cells. ATAC-seq and RNA-seq were conducted to identify differentially accessible regions and differentially expressed genes (DEGs), respectively (P < 0.05, |log2 Fold Change| >1). QRT-PCR was utilized to validate target gene expression.

Results: We identified 100,865 differentially accessible regions, of which 7225 exhibited higher accessibility in IgAN. Functional analysis revealed that these regions are enriched in T lymphocyte activation and immune pathways. ELF3, MEIS1, and NFYC were identified as key TFs associated with IgAN. QRT-PCR indicated a significant upregulation of hub genes including MEIS1 in IgAN.

Conclusion: We identified key TFs and genes by integrating ATAC-seq and RNA-seq, which provide novel therapeutic targets for IgAN and insights into its pathogenesis from an epigenetic perspective.

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http://dx.doi.org/10.1016/j.clim.2025.110432DOI Listing

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