scholarly journals Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase

2019 ◽  
Vol 33 (11-12) ◽  
pp. 620-625 ◽  
Author(s):  
Seongmin Jang ◽  
Chanshin Kang ◽  
Han-Sol Yang ◽  
Taeyang Jung ◽  
Hans Hebert ◽  
...  
Keyword(s):  
Histone H3 ◽  
Structural Basis ◽  
Histone H2b

scholarly journals Structural basis for activation of Dot1L methyltransferase on the nucleosome by histone H2BK120 ubiquitylation

2018 ◽  
Author(s):  
Cathy J Anderson ◽  
Matthew R Baird ◽  
Allen Hsu ◽  
Emily H Barbour ◽  
Yuka Koyama ◽  
...  
Keyword(s):  
Histone H3 ◽  
Point Mutations ◽  
Leukemia Cells ◽  
Structural Basis ◽  
Histone H2b ◽  
Optimal Activity ◽  
A Site ◽  
H3k79 Methylation

Histone H3 lysine 79 (H3K79) methylation is enriched on actively transcribed genes, and its misregulation is a hallmark of leukemia. Methylation of H3K79, which resides on the structured disk face of the nucleosome, is mediated by the Dot1L methyltransferase. Dot1L activity is part of a trans-histone crosstalk pathway, requiring prior histone H2B ubiquitylation of lysine 120 (H2BK120ub) for optimal activity. However, the molecular details describing both how Dot1L binds to the nucleosome and why Dot1L is activated by H2BK120 ubiquitylation are unknown. Here we present the cryo-EM structure of Dot1L bound to a nucleosome reconstituted with a site-specifically ubiquitylated H2BK120. The structure reveals that Dot1L engages the nucleosome acidic patch using an arginine anchor and occupies a conformation poised for methylation. Ubiquitin directly interacts with Dot1L and is positioned as a clamp on the nucleosome interacting region of Dot1L. Using our structure, we identify point mutations that disrupt the nucleosome-specific and ubiquitin-dependent activities of Dot1L. This study establishes a path to better understand Dot1L function in normal and leukemia cells.

scholarly journals Structural basis of recognition and destabilization of histone H2B ubiquitinated nucleosome by DOT1L histone H3 Lys79 methyltransferase

2018 ◽  
Author(s):  
Seongmin Jang ◽  
Chanshin Kang ◽  
Han-Sol Yang ◽  
Taeyang Jung ◽  
Hans Hebert ◽  
...  
Keyword(s):  
Single Molecule ◽  
Cross Talk ◽  
Molecular Basis ◽  
Histone H3 ◽  
Structural Basis ◽  
Histone H2b ◽  
Single Molecule Fret ◽  
Catalytic Function ◽  
Histone H3 Methylation ◽  
Hydrophobic Helix

AbstractDOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B-ubiquitination. Here, we present cryo-EM structures of DOT1L complex with unmodified and H2B-ubiquitinated nucleosomes, showing that DOT1L recognizes H2B-ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L respectively. Furthermore, the structures combined with single-molecule FRET experiment show that H2B-ubiquitination enhances a non-catalytic function of DOT1L destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.

scholarly journals Structural Basis of LSD1-CoREST Selectivity in Histone H3 Recognition

2007 ◽  
Vol 282 (28) ◽  
pp. 20070-20074 ◽  
Author(s):  
Federico Forneris ◽  
Claudia Binda ◽  
Antonio Adamo ◽  
Elena Battaglioli ◽  
Andrea Mattevi
Keyword(s):  
Histone H3 ◽  
Structural Basis

scholarly journals Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation

Science ◽  
2021 ◽  
Vol 371 (6527) ◽  
pp. eabc6663
Author(s):  
Marco Igor Valencia-Sánchez ◽  
Pablo De Ioannes ◽  
Miao Wang ◽  
David M. Truong ◽  
Rachel Lee ◽  
...  
Keyword(s):  
Histone H3 ◽  
Histone H4 ◽  
Histone H2b ◽  
Epigenetic State ◽  
Optimal Maintenance ◽  
H4k16 Acetylation ◽  
H3k79 Methylation ◽  
Regulate Gene

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.

Identification of some heat-induced genes of Trichinella spiralis

Parasitology ◽  
2001 ◽  
Vol 123 (3) ◽  
pp. 293-300 ◽  
Author(s):  
C. H. MAK ◽  
K. W. SUN ◽  
R. C. KO
Keyword(s):  
Stress Proteins ◽  
Trichinella Spiralis ◽  
Histone H3 ◽  
Active Role ◽  
Northern Blotting ◽  
Northern Analysis ◽  
Infective Stage ◽  
Sequencing Data ◽  
Histone H2b ◽  
Induced Genes

Three heat-induced genes of the infective-stage larvae of Trichinella spiralis were successfully identified by the suppression subtractive hybridization (SSH) technique. As indicated by reverse Northern blotting, 19 of 25 clones were scored as differentially transcribed in the heat-shocked infective-stage larvae. The sequencing data showed the presence of 12 different genes. Three were homologous to histone H3, histone H2B and translationally controlled tumour protein (TCTP). A 0.6 kb cDNA of histone H3 was generated by the RACE method and sequenced. It contained an open reading frame of 136 amino acids that demonstrated 94% identity with genes from Drosophila hydei. Semi-quantitative RT-PCR indicated that after heat-shock treatment, the expression levels of histone H3, histone H2B and TCTP increased 4.8, 27 and 5.7-fold, respectively. Northern analysis confirmed the upregulation of histone H3, histone H2B and TCTP transcripts. The upregulation of these genes during stress conditions has not been reported in parasitic organisms. The stress proteins may play an active role to sustain the parasite after exposure to hostile host factors.

scholarly journals Methylation of Histone H3 by COMPASS Requires Ubiquitination of Histone H2B by Rad6

2002 ◽  
Vol 277 (32) ◽  
pp. 28368-28371 ◽  
Author(s):  
Jim Dover ◽  
Jessica Schneider ◽  
Mary Anne Tawiah-Boateng ◽  
Adam Wood ◽  
Kimberly Dean ◽  
...  
Keyword(s):  
Histone H3 ◽  
Histone H2b

scholarly journals Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase

2021 ◽  
Vol 4 (4) ◽  
pp. e202000919
Author(s):  
Cheng-Han Ho ◽  
Yoshimasa Takizawa ◽  
Wataru Kobayashi ◽  
Yasuhiro Arimura ◽  
Hiroshi Kimura ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Essential Role ◽  
Histone H3 ◽  
Underlying Mechanism ◽  
Structural Basis ◽  
Histone H4 ◽  
Nucleosomal Histone

SET8 is solely responsible for histone H4 lysine-20 (H4K20) monomethylation, which preferentially occurs in nucleosomal H4. However, the underlying mechanism by which SET8 specifically promotes the H4K20 monomethylation in the nucleosome has not been elucidated. Here, we report the cryo-EM structures of the human SET8–nucleosome complexes with histone H3 and the centromeric H3 variant, CENP-A. Surprisingly, we found that the overall cryo-EM structures of the SET8–nucleosome complexes are substantially different from the previous crystal structure models. In the complexes with H3 and CENP-A nucleosomes, SET8 specifically binds the nucleosomal acidic patch via an arginine anchor, composed of the Arg188 and Arg192 residues. Mutational analyses revealed that the interaction between the SET8 arginine anchor and the nucleosomal acidic patch plays an essential role in the H4K20 monomethylation activity. These results provide the groundwork for understanding the mechanism by which SET8 specifically accomplishes the H4K20 monomethylation in the nucleosome.

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