Work

NF-κB restrains nutrient-dependent transcription programs through chromatin modulation in Drosophila

Year: 2026

Type: article

Abstract: The co-evolution of immune and metabolic systems has endowed immune signaling pathways with distinct control of cellular metabolism. Innate immune transcription factors, such as nuclear factor κB (NF-κB), have thus emerged as key regulators of adaptive metabolic responses to changes in diet and nutrition. Utilizing chromatin accessibility genomics, we found that Drosophila NF-κB (Relish) can restrain nutrient-dependent metabolic transcriptional programs that control cellular catabolism of energy substrates, divergent from the protein's canonical role as a transcriptional activator. NF-κB/Relish restricts chromatin accessibility through modulating histone acetylation at metabolic target gene loci, which restrains metabolic gene transcription and blocks excessive activation of nutrient-dependent metabolic programs. Targeted genetic screening revealed that histone deacetylase 6 interacts with NF-κB/Relish at NF-κB DNA regulatory motifs to limit chromatin accessibility and repress metabolic transcriptional programs. These results highlight that innate immune transcription factors can epigenetically restrain cellular catabolism to fine-tune nutrient-dependent metabolic adaptation.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf1530

Authors: Xiangshuo Kong, Conghui Li, Jason Karpac

Institution: Texas A&M University

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funder: National Institute of Diabetes and Digestive and Kidney Diseases