IISER MOHALI

Abstract: In multicellular organisms, the organization of the genome into distinct chromatin domains enforces appropriate gene expression patterns during development and underlies the ability of the invariant genome to give rise to a multitude of cell types. The assembly of repressive heterochromatin domains that can self-propagate and be epigenetically inherited across multiple cell divisions is crucial to prevent inappropriate gene expression. However, the key feature that determines self-propagation of heterochromatin remains undefined. Our work has directly implicated methylated histones, specifically tri-methylation of histone H3 lysine 9 (H3K9me3), as carriers of epigenetic information that allow propagation of heterochromatin in a self-templating manner. Importantly, we have shown that epigenetic inheritance of heterochromatin requires a critical density threshold of H3K9me3 to effectively target the histone methyltransferase Clr4/Suv39h, which binds to and catalyzes additional H3K9 methylation (“read-write”) to maintain heterochromatin. I will present our recent discovery of a heterochromatin heritability regulatory hub (HRH) that senses environmental cues and modulates H3K9me3 density to control heterochromatin self-propagation, highlighting its implications for stimulus-responsive changes in heterochromatin heritability and the dynamic reorganization of the epigenetic landscape in physiology and disease.