Evidence map›Paper›PMID 36806146›Full record

ArticleGenome research2023

Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells.

Cui Du, Jing Jiang, Yuzhuo Li, Miao Yu, Jian Jin, Shuai Chen, Hairui Fan, Todd S Macfarlan, Bin Cao, Ming-An Sun

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. CHD8-Dependent Chromatin Licensing Sustains Trophoblast Stem Cell Transcriptional Programs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Review
  4. Genomic-microbial coevolution in human development: chromosome 2 fusion, and human accelerated regions.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Endogenous retrovirus HERVH-derived lncRNAProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024
    Article
  18. Article
  19. 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

10 authors at 4 institutions in 3 countries.

Cui Du *Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Jing Jiang *Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Yuzhuo LiInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Miao YuFujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Jian JinInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Shuai ChenInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Hairui FanInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Todd S MacfarlanThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA.
Bin CaoFujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; mingansun@yzu.edu.cn caobin19@xmu.edu.cn.
Ming-An SunInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; mingansun@yzu.edu.cn caobin19@xmu.edu.cn.ORCID 0000-0002-4661-3027
Yangzhou University · CNXiamen University · CNEunice Kennedy Shriver National Institute of Child Health and Human Development · USMinistry of Education · MV

Funding

Mechanisms of Mammalian Epigenome ReprogrammingZIAHD008933 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MACFARLAN, TODD SCOTT · 2013 to 2025
$19.1M
6 · The paper itself

Abstract

The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggests that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immunity TFs STAT1 and IRF1. Integration of ChIP-seq data confirms the binding of GATA2/3, MSX2, and their related factors on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). MER41-derived enhancers that are constitutively active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of relevant TFs and their subfamily compositions. We further demonstrate that GATA2/3 and MSX2 have prevalent binding to numerous other ERV families - indicating their broad impact on ERV-derived enhancers. Functionally, the derepression of many syncytiotrophoblast genes after MSX2 knockdown is likely to be mediated by regulatory elements derived from ERVs - suggesting ERVs are also important for mediating transcriptional repression. Overall, this study characterizes the regulation of ERV-derived regulatory elements by GATA2/3, MSX2, and their cofactors in human TSCs, and provides mechanistic insights into the importance of ERVs in human trophoblast regulatory network.

Indexed as

Endogenous RetrovirusesAnimalsFemaleGATA2 Transcription FactorGATA3 Transcription FactorHomeodomain ProteinsHumansMammalsPlacentaPregnancyPrimatesRegulatory Sequences, Nucleic AcidStem CellsTrophoblastsGATA2 protein, humanGATA2 Transcription FactorGATA3 protein, humanGATA3 Transcription FactorHomeodomain ProteinsMSX2 protein

Identifiers

PMID36806146
PMCPMC10069462
OpenAlexW4321200688

What OpenQuestion holds

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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.