Evidence map›Paper›PMID 35640156›Full record

ArticleHuman molecular genetics2022

Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4).

Malvin Jefri, Xin Zhang, Patrick S Stumpf, Li Zhang, Huashan Peng, Nuwan Hettige, Jean-Francois Theroux, Zahia Aouabed, Khadija Wilson, Shriya Deshmukh and 9 more

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

Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. 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

19 authors at 6 institutions in 4 countries.

Malvin JefriPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Xin ZhangPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Patrick S StumpfInstitute for Computational Biomedicine, RWTH Aachen University, Aachen 52056, Germany.
Li ZhangMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Huashan PengPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Nuwan HettigePsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Jean-Francois TherouxPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Zahia AouabedPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Khadija WilsonDepartment of Biochemistry and Molecular, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Shriya DeshmukhDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Lilit AntonyanPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Anjie NiPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Shaima AlsuwaidiPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Ying ZhangPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.
Nada JabadoDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Benjamin A GarciaDepartment of Biochemistry and Molecular, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Andreas SchuppertInstitute for Computational Biomedicine, RWTH Aachen University, Aachen 52056, Germany.
Hans T BjornssonMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Carl ErnstPsychiatric Genetics Group, McGill University, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Verdun, Montreal, QC H4H 1R3, Canada.ORCID 0000-0002-2959-221X
Douglas Mental Health University Institute · CAJohns Hopkins University · USRWTH Aachen University · DEWashington University in St. Louis · USMcGill University · CAMcGill University Health Centre · CA

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6M
A Mass Spectrometry Approach to the Genetic and Epigenetic Mechanisms Controlling Neuronal IdentityR01NS111997 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI DAHMANE, NADIA, GARCIA, BENJAMIN A · 2020 to 2024
$2.6M
NCI NIH HHS P01 CA196539
6 · The paper itself

Abstract

Kabuki syndrome is frequently caused by loss-of-function mutations in one allele of histone 3 lysine 4 (H3K4) methyltransferase KMT2D and is associated with problems in neurological, immunological and skeletal system development. We generated heterozygous KMT2D knockout and Kabuki patient-derived cell models to investigate the role of reduced dosage of KMT2D in stem cells. We discovered chromosomal locus-specific alterations in gene expression, specifically a 110 Kb region containing Synaptotagmin 3 (SYT3), C-Type Lectin Domain Containing 11A (CLEC11A), Chromosome 19 Open Reading Frame 81 (C19ORF81) and SH3 And Multiple Ankyrin Repeat Domains 1 (SHANK1), suggesting locus-specific targeting of KMT2D. Using whole genome histone methylation mapping, we confirmed locus-specific changes in H3K4 methylation patterning coincident with regional decreases in gene expression in Kabuki cell models. Significantly reduced H3K4 peaks aligned with regions of stem cell maps of H3K27 and H3K4 methylation suggesting KMT2D haploinsufficiency impact bivalent enhancers in stem cells. Preparing the genome for subsequent differentiation cues may be of significant importance for Kabuki-related genes. This work provides a new insight into the mechanism of action of an important gene in bone and brain development and may increase our understanding of a specific function of a human disease-relevant H3K4 methyltransferase family member.

Indexed as

Histone-Lysine N-MethyltransferaseHistonesVestibular DiseasesAbnormalities, MultipleDNA-Binding ProteinsFaceHematologic DiseasesHumansNeoplasm ProteinsStem CellsDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseHistonesKMT2D protein, humanMLL4 protein, humanNeoplasm Proteins

Identifiers

PMID35640156
PMCPMC9616574
OpenAlexW4281623849

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.