Data from: Bromodomain-containing protein 4 regulates innate inflammation via modulation of alternative splicing (images and qPCR data)
Data files
Jun 15, 2023 version files 35.68 MB
Abstract
Bromodomain-containing Protein 4 (BRD4) is a transcriptional regulator which coordinates gene expression programs controlling cancer biology, inflammation, and fibrosis. In the context of virus-infection, BRD4-specific inhibitors (BRD4i) block the release of pro-inflammatory cytokines and prevent downstream epithelial plasticity. Although the chromatin modifying functions of BRD4 in inducible gene expression have been extensively investigated, its roles in post-transcriptional regulation are not well understood. Given BRD4's interaction with the transcriptional elongation complex and spliceosome, we hypothesize that BRD4 is a functional regulator of mRNA processing. To address this question, we combine data-independent analysis - parallel accumulation-serial fragmentation (diaPASEF) with RNA-sequencing to achieve deep and integrated coverage of the proteomic and transcriptomic landscapes of human small airway epithelial cells exposed to viral challenge and treated with BRD4i. The transcript-level data was further interrogated for alternative splicing analysis, and the resulting datasets were correlated to identify pathways subject to post-transcriptional regulation. We discover that BRD4 regulates alternative splicing of key genes, including Interferon-related Developmental Regulator 1 (IFRD1) and X-Box Binding Protein 1 (XBP1), related to the innate immune response and the unfolded protein response. These findings extend the transcriptional elongation-facilitating actions of BRD4 in control of post-transcriptional RNA processing in innate signaling.
Usage notes
Any image viewer/analysis software (e.g. FIJI), and excel.