Browsing by Author "Piaszyk-Borychowska, Anna"
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Item Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation(2020) Piaszyk-Borychowska, Anna; Bluyssen, Johannes A.R. PromotorAtherosclerosis is a leading cause of mortality world-wide. The key etiological factor is vascular inflammation, mediated by vascular smooth muscle cells and immune cells. Signal Integration (SI) between JAK-STAT and TLR4 signaling pathways plays a crucial role in pro-inflmmatory response. Genome-wide transcriptome (RNA-seq) and genome (ChIP-seq) analysis revealed, that synergistic IFNγ-, IFNα- and LPS-dependent activation of STAT1- and NFκB-containing transcriptional complexes binding to composite GAS/ISRE and NFκB sites in the close proximity on DNA, due to STAT1-dependent open chromatin state, underlies the mechanism of robust pro-inflammatory gene expression in vascular cells. Moreover, it was proposed the mechanism regulating SI between JAK-STAT and TLR4 pathways in the context of pro-inflammatory gene down-regulation, in which STAT1 and NFκB mediate negative histone mark deposition. Next, a role of STAT1 in IFNγ-dependent vascular smooth muscle cell-specific gene expression relying on hierarchical collaboration with cell type-specific transcription factor, was proposed. This research could be used in the future to develop new diagnostic and therapeutical strategies against atherosclerosis.