Work

Induction of the zinc finger transcription factor GATA2 promotes kidney inflammation-related gene expression

Year: 2025

Type: article

Abstract: 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 then performed RNA-seq, Assay for Transposase-Accessible Chromatin (ATAC)-seq, and Cleavage Under Targets and Tagmentation (CUT&Tag). We also conducted ATAC-seq using GATA2-expressing cell fractions sorted from mouse kidney tissues. These comprehensive analyses demonstrated that GATA2 directly upregulates genes associated with kidney inflammation. In particular, GATA2 bound to crucial kidney inflammation-associated gene loci and increased chromatin accessibility at these regions, 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 upregulation 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.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110372

Authors: Jun Takai, Hinata Ueki, Satoshi Uemura

Institution: Tohoku Medical and Pharmaceutical University

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430