Transcriptional condensates at super-enhancers mediate pH-dependent transcriptional control in innate immunity.

ABSTRACT: Tissue acidification is a common feature of hypoxia, inflammation and solid tumor. Acidic pH regulates innate immune response in macrophages by weakening BRD4-containing transcriptional condensates. Yet how disruption of transcriptional condensates leads to gene-specific regulation of immune programs remain unclear. Here, we integrated ATAC-seq, ChIP-seq, and RNA-seq of primary murine macrophages and performed integrative epigenomics analyses to identify transcriptional regulators (TRs) with pH-sensitive regulatory potential and association to BRD4-dependent transcriptional condensates. We determined pH-dependent super-enhancers (SEs) by extended profiles of BRD4 binding and h3K27ac marks. We found RELA, IRF family, and STAT family as candidate TRs enriched at BRD4-associated, pH-sensitive

SUBMITTER: Wang S 

PROVIDER: S-EPMC12636582 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature