7K6P

Active state Dot1 bound to the unacetylated H4 nucleosome

Summary for 7K6P

• Entry DOI: 10.2210/pdb7k6p/pdb
• EMDB information: 22691 22692 22693 22694 22695
• Descriptor: Histone H3.2, Histone H4, Histone H2A type 1, ... (9 entities in total)
• Functional Keywords: structural protein/dna/transferase, transferase, structural protein-dna-transferase complex
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 12
• Total formula weight: 233348.82

Authors

Valencia-Sanchez, M.I.,De Ioannes, P.E.,Miao, W.,Truong, D.M.,Lee, R.,Armache, J.-P.,Boeke, J.D.,Armache, K.-J. (deposition date: 2020-09-21, release date: 2021-02-10, Last modification date: 2024-03-06)

Primary citation

Valencia-Sanchez, M.I.,De Ioannes, P.,Wang, M.,Truong, D.M.,Lee, R.,Armache, J.P.,Boeke, J.D.,Armache, K.J.
Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation.
Science, 371:-, 2021

PubMed Abstract: Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo. These data reveal mechanisms that control H3K79 methylation and demonstrate how H4K16ac, H3K79me, and H2BUb function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state.

PubMed: 33479126
DOI: 10.1126/science.abc6663

Experimental method

ELECTRON MICROSCOPY (3.2 Å)