8GPN

Human menin in complex with H3K79Me2 nucleosome

Summary for 8GPN

• Entry DOI: 10.2210/pdb8gpn/pdb
• EMDB information: 34195
• Descriptor: Histone H3.2, Histone H4, Histone H2A type 1, ... (7 entities in total)
• Functional Keywords: specific histone modification reader, gene regulation
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 11
• Total formula weight: 286557.55

Authors

Lin, J.,Yu, D.,Lam, W.H.,Dang, S.,Zhai, Y.,Li, X.D. (deposition date: 2022-08-26, release date: 2023-02-15, Last modification date: 2023-03-01)

Primary citation

Lin, J.,Wu, Y.,Tian, G.,Yu, D.,Yang, E.,Lam, W.H.,Liu, Z.,Jing, Y.,Dang, S.,Bao, X.,Wong, J.W.H.,Zhai, Y.,Li, X.D.
Menin "reads" H3K79me2 mark in a nucleosomal context.
Science, 379:717-723, 2023

PubMed Abstract: Methylation of histone H3 lysine-79 (H3K79) is an epigenetic mark for gene regulation in development, cellular differentiation, and disease progression. However, how this histone mark is translated into downstream effects remains poorly understood owing to a lack of knowledge about its readers. We developed a nucleosome-based photoaffinity probe to capture proteins that recognize H3K79 dimethylation (H3K79me2) in a nucleosomal context. In combination with a quantitative proteomics approach, this probe identified menin as a H3K79me2 reader. A cryo-electron microscopy structure of menin bound to an H3K79me2 nucleosome revealed that menin engages with the nucleosome using its fingers and palm domains and recognizes the methylation mark through a π-cation interaction. In cells, menin is selectively associated with H3K79me2 on chromatin, particularly in gene bodies.

PubMed: 36795828
DOI: 10.1126/science.adc9318

Experimental method

ELECTRON MICROSCOPY (3.2 Å)