Evidence map›Paper›PMID 33846619›Full record

ArticleNature chemical biology2021

Genome-wide screens uncover KDM2B as a modifier of protein binding to heparan sulfate.

Ryan J Weiss, Philipp N Spahn, Austin W T Chiang, Qing Liu, Jing Li, Kristina M Hamill, Sandra Rother, Thomas M Clausen, Marten A Hoeksema, Bryce M Timm and 6 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2021. 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
2.0field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. EZH2,World journal of stem cells · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Adding a Chemical Biology Twist to CRISPR Screening.Israel journal of chemistry · 2023
    Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Ryan J Weiss *Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-4563-6075
Philipp N Spahn *Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Austin W T ChiangDepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Qing LiuDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Jing LiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Kristina M HamillDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Sandra RotherDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0631-752X
Thomas M ClausenDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Marten A HoeksemaDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5981-121X
Bryce M TimmDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Kamil GodulaDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Yitzhak TorDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Philip L S M GordtsGlycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-7224-4328
Nathan E LewisGlycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA. n4lewis@eng.ucsd.edu.
Jeffrey D EskoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. jesko@health.ucsd.edu.ORCID http://orcid.org/0000-0001-8322-1834
University of California San Diego · USNovo Nordisk Foundation · DKUC San Diego Health System · USUniversity of Copenhagen · DK

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
UCSD Biomedical Scientist Career Development Program in GlycoscienceK12HL141956 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D, GODULA, KAMIL · 2018 to 2022
$5.3M
Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3M
GENETIC CONTROL OF PROTEOGLYCAN METABOLISMR37GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2000 to 2010
$3.9M
LIPID METABOLISM IN ANIMAL CELLSR01GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 1985 to 2019
$3.4M
In vivo glycan engineering at the cell-matrix interface to control stem cell fateDP2HD087954 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GODULA, KAMIL · 2015 to 2015
$2.3M
Genome-wide Analysis of Heparan Sulfate using CRISPR/Cas9R21CA199292 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2015 to 2016
$371k
NCI NIH HHS P30 CA023100NCI NIH HHS R21 CA199292NHLBI NIH HHS K12 HL141956NICHD NIH HHS DP2 HD087954NIGMS NIH HHS R01 GM033063NIGMS NIH HHS R35 GM119850NIGMS NIH HHS R37 GM033063NIGMS NIH HHS T32 GM008326
6 · The paper itself

Abstract

Heparan sulfate (HS) proteoglycans bind extracellular proteins that participate in cell signaling, attachment and endocytosis. These interactions depend on the arrangement of sulfated sugars in the HS chains generated by well-characterized biosynthetic enzymes; however, the regulation of these enzymes is largely unknown. We conducted genome-wide CRISPR-Cas9 screens with a small-molecule ligand that binds to HS. Screening of A375 melanoma cells uncovered additional genes and pathways impacting HS formation. The top hit was the epigenetic factor KDM2B, a histone demethylase. KDM2B inactivation suppressed multiple HS sulfotransferases and upregulated the sulfatase SULF1. These changes differentially affected the interaction of HS-binding proteins. KDM2B-deficient cells displayed decreased growth rates, which was rescued by SULF1 inactivation. In addition, KDM2B deficiency altered the expression of many extracellular matrix genes. Thus, KDM2B controls proliferation of A375 cells through the regulation of HS structure and serves as a master regulator of the extracellular matrix.

Indexed as

Genome-Wide Association StudyAlgorithmsCell Line, TumorCell ProliferationCRISPR-Cas SystemsDrug DiscoveryExtracellular MatrixF-Box ProteinsHeparan SulfateHigh-Throughput Screening AssaysHumansJumonji Domain-Containing Histone DemethylasesProtein BindingRNA-SeqSulfotransferasesF-Box ProteinsHeparan SulfateJumonji Domain-Containing Histone DemethylasesKDM2A protein, humanSULF1 protein, humanSulfotransferases

Identifiers

PMID33846619
PMCPMC8159865
OpenAlexW3154867453

What OpenQuestion holds

Textmetadata
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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.