Evidence map›Paper›PMID 39149911›Full record

ArticleNucleic acids research2024

Ubiquitinated histone H2B as gatekeeper of the nucleosome acidic patch.

Chad W Hicks, Sanim Rahman, Susan L Gloor, James K Fields, Natalia Ledo Husby, Anup Vaidya, Keith E Maier, Michael Morgan, Michael-Christopher Keogh, Cynthia Wolberger

Erratum issuedAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. A Chromatin Biology Assessment of AlphaFold3.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Review
  15. Article
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Chad W HicksDepartment of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Sanim RahmanDepartment of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Susan L GloorEpiCypher Inc., 6 Davis Drive, Suite 755, Durham, NC 27709, USA.
James K FieldsDepartment of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Natalia Ledo HusbyEpiCypher Inc., 6 Davis Drive, Suite 755, Durham, NC 27709, USA.
Anup VaidyaEpiCypher Inc., 6 Davis Drive, Suite 755, Durham, NC 27709, USA.
Keith E MaierEpiCypher Inc., 6 Davis Drive, Suite 755, Durham, NC 27709, USA.
Michael MorganDepartment of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Michael-Christopher KeoghEpiCypher Inc., 6 Davis Drive, Suite 755, Durham, NC 27709, USA.
Cynthia WolbergerDepartment of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.ORCID 0000-0001-8578-2969

Funding

Mechanistic studies of chromatin modification in transcription regulationR35GM130393 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Cynthia Wolberger · 2019 to 2026
$7.3M
Novel enzyme inhibitor screening platform using modified designer nucleosomesR44GM119893 · NIGMS · EPICYPHER, INC. · PI SUN, ZU-WEN · 2019 to 2020
$1.9M
Development of highly specific and renewable chromatin labelling reagentsR43GM134834 · NIGMS · EPICYPHER, INC. · PI JOHNSTONE, ANDREA LYNN · 2019 to 2019
$300k
Regulation and recognition of H3K79meF31CA261154 · NCI · JOHNS HOPKINS UNIVERSITY · PI HICKS, CHAD · 2021 to 2023
$139k
Molecular Basis of Histone Methylation by PRMT5F31CA271743 · NCI · JOHNS HOPKINS UNIVERSITY · PI RAHMAN, SANIM · 2023 to 2025
$117k
Frederick National Laboratory for Cancer Research HSSN261200800001ENCI NIH HHS F31 CA261154NCI NIH HHS F31CA261154NCI NIH HHS F31 CA271743NIGMS NIH HHS R35 GM130393NIGMS NIH HHS R35GM130393NIGMS NIH HHS R43 GM134834NIGMS NIH HHS R44 GM119893NIH HHS R43GM134834
6 · The paper itself

Abstract

Monoubiquitination of histones H2B-K120 (H2BK120ub) and H2A-K119 (H2AK119ub) play opposing roles in regulating transcription and chromatin compaction. H2BK120ub is a hallmark of actively transcribed euchromatin, while H2AK119ub is highly enriched in transcriptionally repressed heterochromatin. Whereas H2BK120ub is known to stimulate the binding or activity of various chromatin-modifying enzymes, this post-translational modification (PTM) also interferes with the binding of several proteins to the nucleosome H2A/H2B acidic patch via an unknown mechanism. Here, we report cryoEM structures of an H2BK120ub nucleosome showing that ubiquitin adopts discrete positions that occlude the acidic patch. Molecular dynamics simulations show that ubiquitin remains stably positioned over this nucleosome region. By contrast, our cryoEM structures of H2AK119ub nucleosomes show ubiquitin adopting discrete positions that minimally occlude the acidic patch. Consistent with these observations, H2BK120ub, but not H2AK119ub, abrogates nucleosome interactions with acidic patch-binding proteins RCC1 and LANA, and single-domain antibodies specific to this region. Our results suggest a mechanism by which H2BK120ub serves as a gatekeeper to the acidic patch and point to distinct roles for histone H2AK119 and H2BK120 ubiquitination in regulating protein binding to nucleosomes.

Indexed as

Cryoelectron MicroscopyHistonesMolecular Dynamics SimulationNucleosomesUbiquitinUbiquitinationHumansProtein BindingProtein Processing, Post-TranslationalHistonesNucleosomesUbiquitin

Identifiers

PMID39149911
PMCPMC11381367

What OpenQuestion holds

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Registered trials

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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.