Evidence map›Paper›PMID 29760402›Full record

ArticleScientific reports2018

Roles of Enhancer RNAs in RANKL-induced Osteoclast Differentiation Identified by Genome-wide Cap-analysis of Gene Expression using CRISPR/Cas9.

Yukako Sakaguchi, Keizo Nishikawa, Shigeto Seno, Hideo Matsuda, Hiroshi Takayanagi, Masaru Ishii

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Fish-Ing for Enhancers in the Heart.International journal of molecular sciences · 2021
    Review
  9. Regulation of Osteoclastogenesis and Bone Resorption by miRNAs.Frontiers in cell and developmental biology · 2021
    Review
  10. 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

6 authors at 3 institutions in 1 country.

Yukako SakaguchiDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Keizo NishikawaDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. nishi@ifrec.osaka-u.ac.jp.
Shigeto SenoDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan.ORCID 0000-0003-3861-6444
Hideo MatsudaDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan.ORCID 0000-0002-4701-3779
Hiroshi TakayanagiDepartment of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Masaru IshiiDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. mishii@icb.med.osaka-u.ac.jp.
Japan Science and Technology Agency · JPThe University of Osaka · JPThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bidirectional transcription has been proposed to play a role associated with enhancer activity. Transcripts called enhancer RNAs (eRNAs) play important roles in gene regulation; however, their roles in osteoclasts are unknown. To analyse eRNAs in osteoclasts comprehensively, we used cap-analysis of gene expression (CAGE) to detect adjacent transcription start sites (TSSs) that were distant from promoters for protein-coding gene expression. When comparing bidirectional TSSs between osteoclast precursors and osteoclasts, we found that bidirectional TSSs were located in the 5'-flanking regions of the Nrp2 and Dcstamp genes. We also detected bidirectional TSSs in the intron region of the Nfatc1 gene. To investigate the role of bidirectional transcription in osteoclasts, we performed loss of function analyses using the CRISPR/Cas9 system. Targeted deletion of the DNA regions between the bidirectional TSSs led to decreased expression of the bidirectional transcripts, as well as the protein-coding RNAs of Nrp2, Dcstamp, and Nfatc1, suggesting that these transcripts act as eRNAs. Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation.

Indexed as

Enhancer Elements, GeneticAnimalsCell DifferentiationCells, CulturedCRISPR-Cas SystemsGene Expression ProfilingGene Expression RegulationMembrane ProteinsMiceNeuropilin-2NFATC Transcription FactorsOsteoclastsPromoter Regions, GeneticRANK LigandRNA CapsTranscription Initiation SiteDcstamp protein, mouseMembrane ProteinsNeuropilin-2Nfatc1 protein, mouseNFATC Transcription FactorsRANK LigandRNA Caps

Identifiers

PMID29760402
PMCPMC5951944
OpenAlexW2799922466

What OpenQuestion holds

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LicenceCC BY
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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.