Evidence map›Paper›PMID 30203048›Full record

ArticleNucleic acids research2018

Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism.

Tibor van Welsem, Tessy Korthout, Reggy Ekkebus, Dominique Morais, Thom M Molenaar, Kirsten van Harten, Deepani W Poramba-Liyanage, Su Ming Sun, Tineke L Lenstra, Rohith Srivas and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Histone H2B ubiquitylation: Connections to transcription and effects on chromatin structure.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024
    Review
  7. Article
  8. Review
  9. Review
  10. The Role of DOT1L in Normal and Malignant Hematopoiesis.Frontiers in cell and developmental biology · 2022
    Review
  11. Review
  12. Signals for antigen-independent differentiation of memory CD8Cellular and molecular life sciences : CMLS · 2021
    Review
  13. Review
  14. DOT1L complex regulates transcriptional initiation in human erythroleukemic cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
  16. Article
  17. Article
  18. DOT1L-controlled cell-fate determination and transcription elongation are independent of H3K79 methylation.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  19. Cancer prevention research (Philadelphia, Pa.) · 2020
    Article
  20. 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

18 authors at 4 institutions in 2 countries.

Tibor van WelsemDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Tessy KorthoutDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Reggy EkkebusDivision of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Dominique MoraisDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Thom M MolenaarDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Kirsten van HartenDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Deepani W Poramba-LiyanageDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Su Ming SunDepartment of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Tineke L LenstraMolecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Rohith SrivasDepartment of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Trey IdekerDepartment of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Frank C P HolstegeMolecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Haico van AttikumDepartment of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Farid El OualidUbiQ Bio B.V., 1098 XH Amsterdam, The Netherlands.
Huib OvaaDivision of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Iris J E StulemeijerDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Hanneke VlamingDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Fred van LeeuwenDivision of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
The Netherlands Cancer Institute · NLLeiden University Medical Center · NLUniversity Medical Center Utrecht · NLUniversity of California San Diego · US

Funding

A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
NIEHS NIH HHS R01 ES014811
6 · The paper itself

Abstract

The histone methyltransferase Dot1 is conserved from yeast to human and methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79 methylation by Dot1 affects gene expression and the response to DNA damage, and is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To gain more insight into the functions of Dot1, we generated genetic interaction maps of increased-dosage alleles of DOT1. We identified a functional relationship between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79 methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose-dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which also caused a negative genetic interaction. The stimulatory effect on H2B ubiquitination was mediated by the N-terminus of Dot1, independent of methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions that are independent of its methyltransferase activity.

Indexed as

UbiquitinationChromatinHistone-Lysine N-MethyltransferaseHistonesNuclear ProteinsProtein BindingProtein Interaction MapsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsChromatinDot1 protein, S cerevisiaeHistone-Lysine N-MethyltransferaseHistonesNuclear ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID30203048
PMCPMC6265471
OpenAlexW2890755971

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.