FBS Colloquia No.420Laboratory of Epigenome Dynamics

Dynamic regulation of H3K9 methylation in mouse early development

Methylation of lysine 9 on histone H3 (H3K9 methylation) is a hallmark histone modification found in transcriptionally repressed regions of the genome. This modification is dynamically maintained through the balance between methyltransferases (such as Suv39h1/2, Setdb1, and G9a) and demethylases (such as the Kdm3 and Kdm4 families). Previous work has shown that H3K9 methylation is not merely a static repressive device but also a dynamic mark that is actively rewritten during development. Indeed, in mouse ES cells lacking multiple methyltransferases, a wide range of developmental genes are simultaneously derepressed, suggesting that H3K9 methylation is broadly involved in the proper progression of the developmental program. In this seminar, I will present the roles of dynamic H3K9 methylation regulation in mouse early development from two perspectives: zygotic genome activation shortly after fertilization, and the higher-order chromatin architecture that supports subsequent differentiation. Through these analyses, I will show that dynamic regulation of H3K9 methylation operates at multiple stages of development, and discuss the regulatory mechanisms that link higher-order chromatin structure, histone modifications, and development.