Epigenetics, bioenergetics, and microRNA coordinate gene-specific reprogramming during acute systemic inflammation

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• Acute systemic inflammation involves distinct proinflammatory, anti-inflammatory, and resolution phases.
• These phases are characterized by significant, predictable shifts in gene expression and metabolism.

Purpose of the Study:

• To review the concept of an integrated bioenergy and epigenetic bridge controlling the temporal phases of acute systemic inflammation.
• To elucidate the molecular mechanisms governing gene expression and metabolic reprogramming during inflammation.

Main Methods:

• Review of emerging concepts in bioenergetics and epigenetics related to inflammation.
• Analysis of the roles of Sirt1, NF-κB pathways (p65 and RelB), and microRNAs (miRNAs) in regulating gene expression.
• Examination of chromatin dynamics, including heterochromatin and euchromatin formation.

Main Results:

• The temporal phases of inflammation are orchestrated by a bioenergy-epigenetic bridge.
• Sirt1 and NF-κB-dependent pathways are crucial for generating facultative heterochromatin and euchromatin.
• Differential miRNA expression contributes to gene-specific reprogramming and regulation of inflammatory genes.

Conclusions:

• Molecular reprogramming circuits and dynamic chromatin landscapes temporally define the course of acute inflammation.
• The integrated bioenergy-epigenetic bridge provides a unifying framework for understanding inflammation dynamics.
• Targeting these epigenetic and bioenergetic mechanisms may offer novel therapeutic strategies for inflammatory diseases.