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

Area of Science:

• Immunology
• Metabolic Regulation
• Epigenetics

Background:

• Immune and metabolic systems co-evolve, with immune signaling pathways controlling cellular metabolism.
• Innate immune transcription factors, such as nuclear factor κB (NF-κB), are key regulators of metabolic adaptation to diet and nutrition.

Purpose of the Study:

• To investigate the role of Drosophila NF-κB (Relish) in regulating nutrient-dependent metabolic transcriptional programs.
• To elucidate the epigenetic mechanisms by which NF-κB controls cellular catabolism and metabolic adaptation.

Main Methods:

• Chromatin accessibility genomics to identify NF-κB's regulatory targets.
• Histone acetylation analysis at metabolic gene loci.
• Targeted genetic screening to identify interacting proteins, such as histone deacetylase 6 (HDAC6).

Main Results:

• Drosophila NF-κB (Relish) restrains nutrient-dependent metabolic transcriptional programs, a role distinct from its canonical activator function.
• NF-κB/Relish restricts chromatin accessibility via histone acetylation modulation, thereby limiting metabolic gene transcription.
• Histone deacetylase 6 (HDAC6) interacts with NF-κB/Relish to repress metabolic transcriptional programs by limiting chromatin accessibility.

Conclusions:

• Innate immune transcription factors can epigenetically restrain cellular catabolism.
• This epigenetic control by NF-κB fine-tunes nutrient-dependent metabolic adaptation.
• The interplay between NF-κB and HDAC6 offers a novel regulatory axis in metabolic control.