Inflammatory metabolite 7α,25-OHC promotes TIMP1 expression in COVID-19 monocytes through synergy effect of SMARCC1/JUND/H3K27ac.

ABSTRACT: Chromatin remodeling factors are involved in the inflammatory responses, contributing to tissue damage and multi-organ dysfunction in COVID-19 patients. However, the underlying mechanisms remain unclear. In this study, high-dimensional analyses of single-cell RNA sequencing and single-cell ATAC sequencing data revealed increased chromatin accessibility at the promoters or enhancers of the pro-inflammatory cytokine tissue inhibitor of metalloproteinase-1 (TIMP1), as well as altered gene transcription profiles in monocytes from COVID-19 patients. Motif enrichment and positive regulators analyses identified SMARCC1, the core subunit of the chromatin remodeling complex, and the transcription factor JUND as positive regulators to co-modulate TIMP1 expression. In-vitro experiments, co-immunoprec

SUBMITTER: Feng Y 

PROVIDER: S-EPMC12095718 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature