Single-Cell Tracing Dissects Regulation of Maintenance and Inheritance of Transcriptional Reinduction Memory

Area of Science:

• Cell Biology
• Genetics
• Molecular Biology

Background:

• Transcriptional memory allows organisms to adapt to recurring environmental cues.
• Mechanisms of transcriptional memory maintenance and inheritance in single cells remain largely unknown.

Purpose of the Study:

• To investigate the regulation and heritability of transcriptional memory in Saccharomyces cerevisiae (yeast).
• To identify genetic factors influencing the inheritance of gene expression memory through cell divisions.

Main Methods:

• Utilized microfluidics and single-cell live imaging to track GAL1 gene expression over multiple generations.
• Employed pedigree analysis to quantify memory maintenance and inheritance.
• Conducted systematic knockout screens to identify genes affecting memory loss or gain.

Main Results:

• Identified novel loss-of-memory mutants impacting the inheritance of transcriptional memory.
• Discovered an elp6Δ mutant exhibiting enhanced memory (gain-of-memory).
• Proposed that decreased histone occupancy at the GAL1 promoter mediates the gain-of-memory phenotype in elp6Δ mutants.

Conclusions:

• Uncovered fundamental principles governing the maintenance and inheritance of gene expression states at the single-cell level.
• Highlighted the role of specific genetic regulators in ensuring transcriptional memory heritability.
• Provided insights into epigenetic mechanisms, such as histone occupancy, influencing gene expression memory.