Evidence map›Paper›PMID 34706774›Full record

ArticleEpigenetics & chromatin2021

The role of MORC3 in silencing transposable elements in mouse embryonic stem cells.

Varsha P Desai, Jihed Chouaref, Haoyu Wu, William A Pastor, Ryan L Kan, Harald M Oey, Zheng Li, Jamie Ho, Kelly K D Vonk, David San Leon Granado and 4 more

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

Article in Epigenetics & chromatin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
6.6field-weighted citation impact, top 4% 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

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Professor Emma Whitelaw, a pioneer of epigenetic inheritance.Frontiers in epigenetics and epigenomics · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Research progress on the dermatomyositis specific autoantibodies and malignancy associated dermatomyositis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. The Role of Transposable Elements in Sexual Development.Frontiers in behavioral neuroscience · 2022
    Review
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

14 authors at 5 institutions in 5 countries.

Varsha P Desai *Department of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Jihed Chouaref *Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Haoyu WuDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
William A PastorDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Ryan L KanDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Harald M OeyThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia.
Zheng LiDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Jamie HoDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Kelly K D VonkDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
David San Leon GranadoDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Michael A ChristopherDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Amander T ClarkDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Steven E JacobsenDepartment of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA. jacobsen@ucla.edu.ORCID 0000-0001-9483-138X
Lucia DaxingerDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. L.Clemens-Daxinger@lumc.nl.ORCID 0000-0001-6557-6201
University of California, Los Angeles · USLeiden University Medical Center · NLHoward Hughes Medical Institute · USRadboud University Nijmegen · NLThe University of Queensland · AU

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Epigenetic gene regulation in ArabidopsisR35GM130272 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JACOBSEN, STEVEN E · 2019 to 2023
$1.6M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA016042NIGMS NIH HHS R35 GM130272
6 · The paper itself

Abstract

backgroundMicrorchidia proteins (MORCs) are involved in epigenetic gene silencing in a variety of eukaryotic organisms. Deletion of MORCs result in several developmental abnormalities and their dysregulation has been implicated in developmental disease and multiple cancers. Specifically, mammalian MORC3 mutations are associated with immune system defects and human cancers such as bladder, uterine, stomach, lung, and diffuse large B cell lymphomas. While previous studies have shown that MORC3 binds to H3K4me3 in vitro and overlaps with H3K4me3 ChIP-seq peaks in mouse embryonic stem cells, the mechanism by which MORC3 regulates gene expression is unknown.

resultsIn this study, we identified that mutation in Morc3 results in a suppressor of variegation phenotype in a Modifiers of murine metastable epialleles Dominant (MommeD) screen. We also find that MORC3 functions as an epigenetic silencer of transposable elements (TEs) in mouse embryonic stem cells (mESCs). Loss of Morc3 results in upregulation of TEs, specifically those belonging to the LTR class of retrotransposons also referred to as endogenous retroviruses (ERVs). Using ChIP-seq we found that MORC3, in addition to its known localization at H3K4me3 sites, also binds to ERVs, suggesting a direct role in regulating their expression. Previous studies have shown that these ERVs are marked by the repressive histone mark H3K9me3 which plays a key role in their silencing. However, we found that levels of H3K9me3 showed only minor losses in Morc3 mutant mES cells. Instead, we found that loss of Morc3 resulted in increased chromatin accessibility at ERVs as measured by ATAC-seq.

conclusionsOur results reveal MORC3 as a novel regulator of ERV silencing in mouse embryonic stem cells. The relatively minor changes of H3K9me3 in the Morc3 mutant suggests that MORC3 acts mainly downstream of, or in a parallel pathway with, the TRIM28/SETDB1 complex that deposits H3K9me3 at these loci. The increased chromatin accessibility of ERVs in the Morc3 mutant suggests that MORC3 may act at the level of chromatin compaction to effect TE silencing.

Indexed as

DNA-Binding ProteinsDNA Transposable ElementsEndogenous RetrovirusesMouse Embryonic Stem CellsAdenosine TriphosphatasesAnimalsChromatinGene SilencingMiceAdenosine TriphosphatasesChromatinDNA-Binding ProteinsDNA Transposable ElementsMORC3 protein, mouseChromatin regulatorsEndogenous retrovirusesIAPsMommeD screenMORC3

Identifiers

PMID34706774
PMCPMC8555065
OpenAlexW3209092046

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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.