Induction of the zinc finger transcription factor GATA2 promotes kidney inflammation-related gene expression
Kidney diseases pose a medical challenge worldwide. Excessive kidney inflammation plays a central role in disease progression. While the transcription factor GATA binding protein 2 (GATA2) is known to govern the hematopoietic system, emerging evidence suggests that it also promotes kidney inflammation. To date, the precise molecular mechanisms underlying GATA2-mediated kidney inflammation remain unclear.Here, we examined the transcriptional landscape, genome-wide GATA2 occupancy, and chromatin accessibility upon GATA2 induction in kidney cells. We generated an inducible GATA2 expression system using a renal tubular cell line and performed RNA-seq, Assay for Transposase-Accessible Chromatin (ATAC)-seq, and Cleavage Under Targets and Tagmentation (CUT&amp;Tag). We also conducted ATAC-seq using GATA2-expressing cell fractions sorted from mouse kidney tissues. These genome-wide analyses demonstrated that inducible GATA2 expression up-regulates genes associated with kidney inflammation. GATA2 also increases chromatin accessibility at crucial kidney inflammation-associated gene loci, including colony-stimulating factor 1 (Csf1), C-X-C motif chemokine ligand 10 (Cxcl10), and vascular cell adhesion molecule-1 (Vcam1). Motif analysis revealed that the binding sequences of the activator protein-1 (AP-1), an inflammation-induced transcription factor, are frequently located adjacent to genomic regions where GATA2 increases chromatin accessibility. Furthermore, the up-regulation of Csf1, Cxcl10, and Vcam1 following GATA2 induction was attenuated by the AP-1-specific inhibitor T-5224.Overall, this study is the first to determine genome-wide GATA2 occupancy and its impact on chromatin accessibility in kidney cells. These findings provide molecular insights into the role of GATA2 in kidney inflammation.