Multi-omics analysis reveals coordinated transcriptional and epigenetic remodeling of tenocytes under IL-1β-driven inflammatory stimulation
- 1Department of Laboratory Medicine, Taizhou First People’s Hospital (Taizhou University Affiliated First People’s Hospital), School of Medicine, Taizhou University
- 2School of Medicine, Taizhou University
Abstract
Background: Tendinopathy is frequently associated with chronic inflammation driven by pro-inflammatory cytokines. Among these, interleukin-1β (IL-1β) serves as a central mediator of tendon degradation, yet its genome-scale transcriptional and epigenetic consequences in tenocytes remain incompletely characterized.
Methods: We profiled the transcriptomes and chromatin accessibility landscapes of control and IL-1β-treated primary rat tenocytes using RNA-seq and ATAC-seq, respectively. Differential expression and accessibility analyses, region-associated differentially expressed gene (RAD) analysis, gene functional enrichment analysis, and transcription factor motif enrichment analysis were performed to delineate the regulatory mechanisms underlying IL-1β-induced cellular response.
Results: IL-1β elicited a profound transcriptional alteration, with 1, 468 differentially expressed genes (811 upregulated and 657 downregulated). Upregulated genes were enriched for immune and inflammatory response pathways, whereas downregulated genes encompassed tendon-specific matrix programs and broader mesenchymal developmental pathways. Concordantly, ATAC-seq revealed 15, 257 differentially accessible regions, with a striking asymmetry toward increased accessibility under IL-1β treatment. Integrative analysis revealed a potential association between chromatin remodeling and transcriptional alterations. Motif enrichment within IL-1β-high accessible regions (IL-1β-HARs) identified C/EBP and NF-κB family members as candidate regulators of inflammatory gene activation, while control-HARs (Ctrl-HARs) harbored motifs for homeostatic transcription factors.
Conclusions: These findings demonstrate that IL-1β affects tenocyte homeostasis by simultaneously activates inflammatory gene programs and suppresses tendon-associated expression through coordinated transcriptional and epigenetic remodeling. The transcription factor regulatory elements identified here provide a mechanistic hint for future investigation, and we hypothesize that targeting these elements may offer a potential therapeutic strategy for inflammatory tendon disorders, while this possibility remains to be tested experimentally.
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BibTeX
@article{zhou2026multiomics,
title = {{Multi-omics analysis reveals coordinated transcriptional and epigenetic remodeling of tenocytes under IL-1β-driven inflammatory stimulation}},
author = {Wenyan Zhou and Xiaonan Wang and Junxin Lin and Zaixing Yang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1940588},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940588/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-omics analysis reveals coordinated transcriptional and epigenetic remodeling of tenocytes under IL-1β-driven inflammatory stimulation
AU - Wenyan Zhou
AU - Xiaonan Wang
AU - Junxin Lin
AU - Zaixing Yang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1940588
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940588/full
AB - Background: Tendinopathy is frequently associated with chronic inflammation driven by pro-inflammatory cytokines. Among these, interleukin-1β (IL-1β) serves as a central mediator of tendon degradation, yet its genome-scale transcriptional and epigenetic consequences in tenocytes remain incompletely characterized. Methods: We profiled the transcriptomes and chromatin accessibility landscapes of control and IL-1β-treated primary rat tenocytes using RNA-seq and ATAC-seq, respectively. Differential expression and accessibility analyses, region-associated differentially expressed gene (RAD) analysis, gene functional enrichment analysis, and transcription factor motif enrichment analysis were performed to delineate the regulatory mechanisms underlying IL-1β-induced cellular response. Results: IL-1β elicited a profound transcriptional alteration, with 1, 468 differentially expressed genes (811 upregulated and 657 downregulated). Upregulated genes were enriched for immune and inflammatory response pathways, whereas downregulated genes encompassed tendon-specific matrix programs and broader mesenchymal developmental pathways. Concordantly, ATAC-seq revealed 15, 257 differentially accessible regions, with a striking asymmetry toward increased accessibility under IL-1β treatment. Integrative analysis revealed a potential association between chromatin remodeling and transcriptional alterations. Motif enrichment within IL-1β-high accessible regions (IL-1β-HARs) identified C/EBP and NF-κB family members as candidate regulators of inflammatory gene activation, while control-HARs (Ctrl-HARs) harbored motifs for homeostatic transcription factors. Conclusions: These findings demonstrate that IL-1β affects tenocyte homeostasis by simultaneously activates inflammatory gene programs and suppresses tendon-associated expression through coordinated transcriptional and epigenetic remodeling. The transcription factor regulatory elements identified here provide a mechanistic hint for future investigation, and we hypothesize that targeting these elements may offer a potential therapeutic strategy for inflammatory tendon disorders, while this possibility remains to be tested experimentally.
SN - 1664-3224
ER -