ArticleCell reports2022
DOT1L activity in leukemia cells requires interaction with ubiquitylated H2B that promotes productive nucleosome binding.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Effect of the Proteasome Inhibitor, Bortezomib, on Histone Modifications in Human Leukemic Cell Lines.International journal of molecular sciences · 2026Article
- Epigenetic Regulation in Acute Myeloid Leukemia: Molecular Mechanisms and Clinical Implications.Cancers · 2026Review
- Histone modification cross-talk: analytical tools and molecular mechanisms.The Biochemical journal · 2026Review
- Roles of histone chaperone Nap1 and histone acetylation in regulating phase-separation of nucleosome arrays.Nature communications · 2025Article
- An Intrinsically Disordered Region of Histone Demethylase KDM5A Activates Catalysis Through Interactions With the Nucleosomal Acidic Patch and DNA.Journal of molecular biology · 2025Article
- Post-translational modification of H2B C-terminal helix regulates nucleosome interactions and chromatin signaling.Nucleic acids research · 2025Article
- The ABCs of the H2Bs: The histone H2B sequences, variants, and modifications.Trends in genetics : TIG · 2025Review
- An intrinsically disordered region of histone demethylase KDM5A activates catalysis through interactions with the nucleosomal acidic patch and DNA.bioRxiv : the preprint server for biology · 2025Article
- Histone modifications and metabolic reprogramming in tumor-associated macrophages: a potential target of tumor immunotherapy.Frontiers in immunology · 2025Review
- Ubiquitinated histone H2B as gatekeeper of the nucleosome acidic patch.Nucleic acids research · 2024Article
- H3K18 & H3K23 acetylation directs establishment of MLL-mediated H3K4 methylation.bioRxiv : the preprint server for biology · 2024Article
- Methods to investigate nucleosome structure and dynamics with single-molecule FRET.Methods (San Diego, Calif.) · 2023Article
- Structural basis of paralog-specific KDM2A/B nucleosome recognition.Nature chemical biology · 2023Article
- Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.Journal of pharmaceutical analysis · 2023Review
- The Effects of Histone H2B Ubiquitylations on the Nucleosome Structure and Internucleosomal Interactions.Biochemistry · 2022Article
- Time Resolved-Fluorescence Resonance Energy Transfer platform for quantitative nucleosome binding and footprinting.Protein science : a publication of the Protein Society · 2022Article
- Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.Frontiers in genetics · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
DOT1L methylates histone H3 lysine 79 during transcriptional elongation and is stimulated by ubiquitylation of histone H2B lysine 120 (H2BK120ub) in a classical trans-histone crosstalk pathway. Aberrant genomic localization of DOT1L is implicated in mixed lineage leukemia (MLL)-rearranged leukemias, an aggressive subset of leukemias that lacks effective targeted treatments. Despite recent atomic structures of DOT1L in complex with H2BK120ub nucleosomes, fundamental questions remain as to how DOT1L-ubiquitin and DOT1L-nucleosome acidic patch interactions observed in these structures contribute to nucleosome binding and methylation by DOT1L. Here, we combine bulk and single-molecule biophysical measurements with cancer cell biology to show that ubiquitin and cofactor binding drive conformational changes to stimulate DOT1L activity. Using structure-guided mutations, we demonstrate that ubiquitin and nucleosome acidic patch binding by DOT1L are required for cell proliferation in the MV4; 11 leukemia model, providing proof of principle for MLL targeted therapeutic strategies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.