Structural highlights
Function
H32_XENLA Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Publication Abstract from PubMed
The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the detailed mechanism is not understood. We report cryo-EM structures of human Dot1L bound to (1) H2BK120Ub and (2) unmodified nucleosome substrates at 3.5 A and 4.9 A, respectively. Comparison of both structures, complemented with biochemical experiments, provides critical insights into the mechanism of Dot1L stimulation by H2BK120Ub. Both structures show Dot1L binding to the same extended surface of the histone octamer. In yeast, this surface is used by silencing proteins involved in heterochromatin formation, explaining the mechanism of their competition with Dot1. These results provide a strong foundation for understanding conserved crosstalk between histone modifications found at actively transcribed genes and offer a general model of how ubiquitin might regulate the activity of chromatin enzymes.
Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination.,Valencia-Sanchez MI, De Ioannes P, Wang M, Vasilyev N, Chen R, Nudler E, Armache JP, Armache KJ Mol Cell. 2019 Apr 8. pii: S1097-2765(19)30233-3. doi:, 10.1016/j.molcel.2019.03.029. PMID:30981630[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Valencia-Sanchez MI, De Ioannes P, Wang M, Vasilyev N, Chen R, Nudler E, Armache JP, Armache KJ. Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination. Mol Cell. 2019 Apr 8. pii: S1097-2765(19)30233-3. doi:, 10.1016/j.molcel.2019.03.029. PMID:30981630 doi:http://dx.doi.org/10.1016/j.molcel.2019.03.029
