Synergism between Chromatin Dynamics and Gene Transcription Enhances Robustness and Stability of Epigenetic Cell Memory

Apart from carrying hereditary information inherited from their ancestors and being able to pass on the information to their descendants, cells can also inherit and transmit information that is not stored as changes in their genome sequence. Such epigenetic cell memory, which is particularly important in multicellular organisms, involves multiple biochemical modules mainly including chromatin organization, epigenetic modification and gene transcription. The synergetic mechanism among these three modules remains poorly understood and how they collaboratively affect the robustness and stability of epigenetic memory is unclear either. Here we developed a multiscale model to address these questions. We found that the chromatin organization driven by long-range epigenetic modifications can significantly enhance epigenetic cell memory and its stability in contrast to that driven by local interaction and that chromatin topology and gene activity can promptly and simultaneously respond to changes in nucleosome modifications while maintaining the robustness and stability of epigenetic cell memory over several cell cycles. We concluded that the synergism between chromatin dynamics and gene transcription facilitates the faithful inheritance of epigenetic cell memory across generations.