Molecular Architecture of heterochromatin formation by human heterochromatin protein 1

Internal Seminar: Yoshimasa Takizawa, Postdoctoral Researcher, Molecular Cryo-Electron Microscopy Unit (Wolf Unit)

Title: Molecular Architecture of heterochromatin formation by human heterochromatin protein 1

Abstract: Can you believe that there is over 2 meters of human genomic DNA in10 µm of each nucleus? To organize the huge amount of genomic DNA, the formation of chromatin is crucial in eukaryotes. The fundamental unit of chromatin is the nucleosome, in which ~147 base-pairs of DNA are wrapped around the histone octamer composed of two copies each of histones H2A, H2B, H3 and H4. Heterochromatin is a condensed higher order chromatin form, and regulates suppression of genomic DNA activities. To form the heterochromatin, heterochromatin protein 1 (HP1) must bind to trimethylated lysine 9 of histone H3 (H3K9me3), which is the epigenetic maker of heterochromatin. However, the formation of heterochromatin by HP1 has not been clear. To elucidate the molecular architecture of heterochromatin, we determined the 3D structure of H3K9me3-containing dinucleosome complex with human HP1 by single particle cryo-electron microscopy (cryo-EM) using a Volta phase plate. Cryo-EM is a powerful technique to obtain 3D structures from samples embedded in vitrified ice in its near-native state, and therefore it is suitable for samples, which are difficult to crystalize, like the dinucleosome-HP1 complex. Our cryo-EM structure shows that the HP1 dimer bridges two H3K9me3 nucleosomes, and that the linker DNA connecting two nucleosomes does not directly associate with HP1. This work now enables us to propose novel features of the heterochromatin unit, and provides insight into the mechanism of heterochromatin formation in eukaryotes.

Refreshments will be served afterwards. We hope to see you there!

Sincerely,

Internal Seminar Organizing Committee:

Bianca Sieveritz

Rob Campbell

Maggi Mars-Brisbin

Yunhui Zheng

Jonathan Ward

Lauren Dembeck

Jigyasa Arora

Maéva Techer