7xd1 Citations

H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity.

Nat Chem Biol (2022)
Related entries: 7xcr, 7xct, 7xd0

Cited: 14 times
EuropePMC logo PMID: 35739357

Abstract

Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the central focus. Here our study on the crosstalk between H2BK34ub and Dot1L-catalyzed H3K79me suggests a novel mechanism of ubiquitination-induced nucleosome distortion to stimulate the activity of an enzyme. We determined the cryo-electron microscopy structures of Dot1L-H2BK34ub nucleosome complex and the H2BK34ub nucleosome alone. The structures reveal that H2BK34ub induces an almost identical orientation and binding pattern of Dot1L on nucleosome as H2BK120ub, which positions Dot1L for the productive conformation through direct ubiquitin-enzyme contacts. However, H2BK34-anchored ubiquitin does not directly interact with Dot1L as occurs in the case of H2BK120ub, but rather induces DNA and histone distortion around the modified site. Our findings establish the structural framework for understanding the H2BK34ub-H3K79me trans-crosstalk and highlight the diversity of mechanisms for histone ubiquitination to activate chromatin-modifying enzymes.

Articles - 7xd1 mentioned but not cited (3)

  1. Histone divergence in trypanosomes results in unique alterations to nucleosome structure. Deák G, Wapenaar H, Sandoval G, Chen R, Taylor MRD, Burdett H, Watson JA, Tuijtel MW, Webb S, Wilson MD. Nucleic Acids Res 51 7882-7899 (2023)
  2. BRCA1-BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes. Burdett H, Foglizzo M, Musgrove LJ, Kumar D, Clifford G, Campbell LJ, Heath GR, Zeqiraj E, Wilson MD. Nucleic Acids Res 51 11080-11103 (2023)
  3. The expedient, CAET-assisted synthesis of dual-monoubiquitinated histone H3 enables evaluation of its interaction with DNMT1. Li Z, Tong Z, Gong Q, Ai H, Peng S, Chen C, Chu GC, Li JB. Chem Sci 14 5681-5688 (2023)


Reviews citing this publication (5)

  1. The ubiquitin codes in cellular stress responses. Sheng X, Xia Z, Yang H, Hu R. Protein Cell 15 157-190 (2024)
  2. Diverse modes of regulating methyltransferase activity by histone ubiquitination. Fields JK, Hicks CW, Wolberger C. Curr Opin Struct Biol 82 102649 (2023)
  3. Interrogating epigenetic mechanisms with chemically customized chromatin. Hananya N, Koren S, Muir TW. Nat Rev Genet 25 255-271 (2024)
  4. Mesenchymal stem cells under epigenetic control - the role of epigenetic machinery in fate decision and functional properties. Walewska A, Janucik A, Tynecka M, Moniuszko M, Eljaszewicz A. Cell Death Dis 14 720 (2023)
  5. Synthesis of ubiquitinated proteins for biochemical and functional analysis. Kriegesmann J, Brik A. Chem Sci 14 10025-10040 (2023)

Articles citing this publication (6)