We have discovered previously that heterochromatin can promote its own assembly in a self-templating manner, leading to epigenetic inheritance of silenced chromatin state in cis through mitosis and meiosis1. Moreover, our work has revealed that the ability of Clr4 to both catalyze H3K9 methylation (“write”) and bind to H3K9me (“read”) is critical for the inheritance of heterochromatin2. However, how epigenetic memory (such as H3K9me) is transmitted to sister chromatids through replication was not known3. By performing a genetic screen for factors uniquely required for heterochromatin inheritance, rather than for de novo assembly, we have identified factors that suppresses turnover of “old” parental histones, particularly in dividing cells, to facilitate epigenetic transmission of heterochromatin. These factors also suppress histone turnover at several euchromatic loci to prevent R-loop formation, ensuring proper replication progression. Our work reveals that suppression of nucleosome turnover is critical to heterochromatin inheritance, and prevents the formation of structural barriers that impede replication at fragile sites. Our recent work on the assembly and maintenance of heterochromatin structures will be presented.
1 . Hall, I. M., Grewal, S. I. S. et al. Establishment and maintenance of a heterochromatin domain. Science 297, 2232-2237 (2002).
2 . Zhang, K., Mosch, K., Fischle, W. & Grewal, S. I. S. Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nat. Struct. Mol. Biol. 1 . , 381-388 (2008).
3 . Taneja, N., Zofall, M., Balachandran, V., Thillainadesan, G., Sugiyama, T., Wheeler, D., Zhou, M., and Grewal, S.I.S. (2017). SNF2 family protein Fft3 suppresses nucleosome turnover to promote epigenetic inheritance and proper replication. Mol. Cell 66: 50-62.