Integration of genetic and chromatin modification data pinpoints autoimmune-specific remodeling of enhancer landscape in CD4 + T cells.

Autor:	Daga N; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Servaas NH; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Kisand K; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Moonen D; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Arnold C; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Reyes-Palomares A; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Kaleviste E; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Kingo K; Department of Dermatology and Venerology, Faculty of Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia and Dermatology Clinic, Tartu University Hospital, Tartu, Estonia., Kuuse R; Department of Internal Medicine, Tartu University Hospital, Tartu, Estonia., Ulst K; Department of Internal Medicine, Tartu University Hospital, Tartu, Estonia., Steinmetz L; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany; Department of Genetics, Stanford University, Stanford, CA, USA., Peterson P; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Nakic N; Functional Genomics, Medicinal Science and Technology, GSK R&D, Stevenage, UK., Zaugg JB; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. Electronic address: judith.zaugg@embl.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Oct 22; Vol. 43 (10), pp. 114810. Date of Electronic Publication: 2024 Oct 09.
DOI:	10.1016/j.celrep.2024.114810
Abstrakt:	CD4 + T cells play a crucial role in adaptive immune responses and have been implicated in the pathogenesis of autoimmune diseases (ADs). Despite numerous studies, the molecular mechanisms underlying T cell dysregulation in ADs remain incompletely understood. Here, we used chromatin immunoprecipitation (ChIP)-sequencing of active chromatin and transcriptomic data from CD4 + T cells of healthy donors and patients with systemic lupus erythematosus (SLE), psoriasis, juvenile idiopathic arthritis (JIA), and Graves' disease to investigate the role of enhancers in AD pathogenesis. By generating enhancer-based gene regulatory networks (eGRNs), we identified disease-specific dysregulated pathways and potential downstream target genes of enhancers harboring AD-associated single-nucleotide polymorphisms (SNPs), which we also validated using chromatin-capture (HiC) data and CRISPR interference (CRISPRi) in primary CD4 + T cells. Our results suggest that alterations in the regulatory landscapes of CD4 + T cells, including enhancers, contribute to the development of ADs and provide a basis for developing new therapeutic approaches. Competing Interests: Declaration of interests The authors declare no conflict of interest. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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