RT Journal Article
T1 Integration of genetic and chromatin modification data pinpoints autoimmune-specific remodeling of enhancer landscape in CD4+ T cells
A1 Daga, Neha
A1 Servaas, Nila H.
A1 Kisand, Kai
A1 Moonen, Dewi
A1 Arnold, Christian
A1 Reyes-Palomares, Armando
A1 Kaleviste, Epp
A1 Kingo, Külli
A1 Kuuse, Reet
A1 Ulst, Katrin
A1 Steinmetz, Lars
A1 Peterson, Pärt
A1 Nakic, Nikolina
A1 Zaugg, Judith B.
K1 Epigenética
K1 Linfocitos
K1 Inmunología
AB 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.
PB Cell Press
YR 2024
FD 2024-10
LK https://hdl.handle.net/10630/41496
UL https://hdl.handle.net/10630/41496
LA eng
NO Daga, Neha et al. Integration of genetic and chromatin modification data pinpoints autoimmune-specific remodeling of enhancer landscape in CD4+ T cells. Cell Reports, 43 (10), 114810 (2024). https://doi.org/10.1016/j.celrep.2024.114810
NO Highlights:- Enhancers and transcription factors in CD4 T cells show autoimmune-disease-specific activity- Enhancer-mediated gene regulatory networks integrate divers types of disease evidence- Disease-specific networks pinpoint disease-relevant enhancers and their target genes- One disease-specific enhancer co-regulates ICOS/CD28/CTL4A, as validated by CRISPRi
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026