Histone methylation codes involved in stemness, multipotency, and senescence in budding tunicates

Area of Science:

• Epigenetics
• Developmental Biology
• Cellular Biology

Background:

• Histone modifications, particularly trimethylation, play crucial roles in regulating gene expression during cellular processes.
• The tunicate Polyandrocarpa misakiensis serves as a model organism for studying cell differentiation and aging.
• Histone H3 lysine 27 trimethylation (H3K27me3) is generally associated with gene silencing and cellular differentiation.

Purpose of the Study:

• To investigate the role of histone H3 trimethylation dynamics in cell differentiation and aging in the tunicate Polyandrocarpa misakiensis.
• To elucidate the function of the budding-specific factor TC14-3 in regulating H3K27me3 and cellular fate.
• To understand the interplay between H3K27me3, H3K4me3, and cellular states like stemness and senescence.

Main Methods:

• Western blotting to detect global H3K27me3 levels.
• Chromatin immunoprecipitation (ChIP) to assess H3K27me3 and H3K4me3 enrichment at specific gene loci.
• Analysis of gene expression patterns related to differentiation and mitochondrial activity.
• Inhibition studies using an H3K27me3 inhibitor.

Main Results:

• Strong H3K27me3 signals were observed in multipotent cells and decreased in senescent adult zooids, but reappeared in buds.
• The budding-specific factor TC14-3 restored H3K27me3 and mitochondrial activity in aging cells, suggesting a role in cell longevity.
• TC14-3 enhanced H3K27me3 of transdifferentiation genes, leading to their downregulation.
• H3K4me3 transiently appeared in bud cells and stably in undifferentiated adult cells, associated with stemness.
• Absence of H3K27me3 and H3K4me3 signals correlated with cellular senescence.

Conclusions:

• TC14-3 driven H3K27 trimethylation acts as a histone code for cell longevity in P. misakiensis.
• Dual H3K27me3 and H3K4me3 signals are linked to cell stemness.
• The dynamic regulation of H3K27me3 and H3K4me3 is critical for maintaining cellular states and preventing senescence.