3 May 2024
Domitilla Del Vecchio
Departments of Mechanical Engineering and Biological Engineering
MIT
DNA methylation and histone modifications mediate the long-term maintenance of gene expression states. Current belief, supported by data from knock-in reporter systems, is that these modifications are established in an all-or-none fashion, thereby making long-term memory an exclusive attribute of silenced and active gene states. We tracked the temporal dynamics of a chromosomally integrated reporter system with clonal resolution to investigate whether these modifications can also enable memory of any gene expression level, and thus equip cells with analog memory. Surprisingly in the context of existing data, we found that cells can maintain intermediate gene expression levels by grades of DNA methylation that remain stable over time. Our nucleosome modification model recapitulates this result when H3K9me3 does not catalyze the recruitment of DNA methylation and the remaining DNA methylation kinetics are slow. The observation that long-term memory is possible for any gene expression level deepens our understanding of epigenetic cell memory and broadens our view of what constitutes a cell type.