Evidence map›Paper›PMID 26240340›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Identification of a functional hotspot on ubiquitin required for stimulation of methyltransferase activity on chromatin.

Matthew T Holt, Yael David, Sam Pollock, Zhanyun Tang, Jongcheol Jeon, Jaehoon Kim, Robert G Roeder, Tom W Muir

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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

27 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. A promiscuous split intein with expanded protein engineering applications.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Matthew T HoltLaboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, NY 10065;
Yael DavidDepartment of Chemistry, Princeton University, Princeton, NJ 08544;
Sam PollockDepartment of Chemistry, Princeton University, Princeton, NJ 08544;
Zhanyun TangLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065;
Jongcheol JeonDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Jaehoon KimDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Robert G RoederLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065;
Tom W MuirDepartment of Chemistry, Princeton University, Princeton, NJ 08544; muir@princeton.edu.
Princeton University · USRockefeller University · USKorea Advanced Institute of Science and Technology · KR

Funding

Nuclear Receptor Coactivator Functions and MechanismsR01DK071900 · NIDDK · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2005 to 2015
$5.9M
Structure, Function and Applications of InteinsR37GM086868 · NIGMS · PRINCETON UNIVERSITY · PI MUIR, TOM · 2012 to 2021
$5.4M
Mechanisms of p53 target gene activation in DNA damage responsesR01CA129325 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2007 to 2011
$4.0M
Development and Applications of 'Designer Chromatin'R01GM107047 · NIGMS · PRINCETON UNIVERSITY · PI MUIR, TOM · 2013 to 2016
$1.2M
NCI NIH HHS CA 129325NCI NIH HHS R01 CA129325NIDDK NIH HHS DK071900NIDDK NIH HHS R01 DK071900NIGMS NIH HHS R01 GM107047NIGMS NIH HHS R37 GM086868NIGMS NIH HHS R37-GM086868
6 · The paper itself

Abstract

Ubiquitylation of histone H2B at lysine 120 (H2B-Ub) plays a critical role in transcriptional elongation, chromatin conformation, as well as the regulation of specific histone H3 methylations. Herein, we report a strategy for the site-specific chemical attachment of ubiquitin to preassembled nucleosomes. This allowed expedited structure-activity studies into how H2B-Ub regulates H3K79 methylation by the methyltransferase human Dot1. Through an alanine scan of the ubiquitin surface, we identified a functional hotspot on ubiquitin that is required for the stimulation of human Dot1 in vitro. Importantly, this result was validated in chromatin from isolated nuclei by using a synthetic biology strategy that allowed selective incorporation of the hotspot-deficient ubiquitin mutant into H2B. The ubiquitin hotspot additionally impacted the regulation of ySet1-mediated H3K4 methylation but was not required for H2B-Ub-induced impairment of chromatin fiber compaction. These data demonstrate the utility of applying chemical ligation technologies to preassembled chromatin and delineate the multifunctionality of ubiquitin as a histone posttranslational modification.

Indexed as

Amino Acid SequenceChromatinEpigenesis, GeneticHistone-Lysine N-MethyltransferaseHistonesHumansLysineMethylationMethyltransferasesMutationNucleosomesProtein BindingProtein EngineeringProtein Processing, Post-TranslationalSequence Homology, Amino AcidSoftwareChromatinDOT1L protein, humanHistone-Lysine N-MethyltransferaseHistonesLysineMethyltransferasesNucleosomesUbiquitinchromatinDot1Lepigeneticsprotein chemistryubiquitin

Identifiers

PMID26240340
PMCPMC4547310
OpenAlexW2099508007

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.