Butyrate Selectively Targets Super-Enhancers and Transcriptional Networks Associated with Human Mast Cell Function

Area of Science:

• Immunology
• Epigenetics
• Cell Biology

Background:

• Mast cells are central mediators of allergic inflammation.
• Butyrate, a short-chain fatty acid from dietary fibers, has been shown to inhibit human mast cell activation.
• The precise molecular mechanisms of butyrate's inhibitory effects on mast cells remain to be fully elucidated.

Purpose of the Study:

• To investigate the underlying mechanisms by which butyrate modulates human mast cell activity.
• To characterize the genome-wide epigenomic impact of butyrate on mast cell gene expression.
• To identify key regulatory elements targeted by butyrate in mast cells.

Main Methods:

• Primary human mast cells were treated with butyrate.
• Integrated transcriptome and histone acetylation (H3K27Ac) profiling was performed.
• The impact of butyrate on gene expression and epigenomic landscapes was analyzed.
• Pharmacological bromodomain inhibition was used to perturb super-enhancer activity.

Main Results:

• Butyrate selectively affected gene expression and regulatory elements in mast cells.
• Key findings include hypoacetylation of promoters and super-enhancers controlling mast cell identity genes.
• Inhibition of super-enhancer activity mimicked butyrate's suppressive effects on mast cell degranulation and gene expression.

Conclusions:

• Butyrate inhibits human mast cell activity by selectively targeting super-enhancers.
• This epigenetic regulation impacts the core transcriptional program of mast cells.
• Butyrate represents a potential therapeutic strategy for allergic inflammation by modulating mast cell epigenetics.