H3K18 lactylation marks tissue-specific active enhancers

Area of Science:

• Epigenetics
• Molecular Biology
• Biochemistry

Background:

• Histone lactylation is a newly identified histone post-translational modification.
• It bridges cellular metabolism and epigenetic regulation.
• Its functional significance is currently under investigation.

Purpose of the Study:

• To generate genome-wide datasets of H3K18la distribution.
• To compare H3K18la profiles with other histone modifications and gene expression.
• To elucidate the role of H3K18la in epigenetic regulation.

Main Methods:

• Genome-wide profiling of H3K18la in mouse embryonic stem cells, macrophages, adipocytes, and skeletal muscle (mouse and human).
• Comparative analysis with established histone modifications (H3K27ac, H3K4me3) and gene expression data.
• Bioinformatic analyses (supervised and unsupervised) to identify distribution patterns.

Main Results:

• Global H3K18la distribution patterns resemble H3K27ac, with distinct differences observed.
• H3K18la marks active promoters of highly expressed genes, including housekeeping genes, across multiple tissues.
• H3K18la positively correlates with H3K27ac, H3K4me3, and gene expression levels.
• Enrichment of H3K18la at active enhancers near functionally important genes was noted.

Conclusions:

• H3K18la serves as a marker for active gene promoters.
• H3K18la also functions as a mark for tissue-specific active enhancers.
• These findings highlight H3K18la's role in linking metabolism to gene expression and tissue-specific functions.