Description:

The Simpson Querrey Institute for Epigenetics presents:

Shiv Grewal, PhD

Biochemistry and Molecular Biology
Center for Cancer Research, NCI 
National Institutes of Health

"The Molecular Basis for Heterochromatin Assembly and Epigenetic Inheritance"

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 a single 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 directly implicates 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 find that epigenetic inheritance of heterochromatin requires maintaining 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.  In addition to discussing our latest findings about how cells maintain the critical density of H3K9me3 and its associated Clr4/Suv39h methyltransferase to epigenetically propagate heterochromatin, I will highlight implications of our work for transgenerational inheritance of epigenetic memory.