Evidence map›Paper›PMID 26935580›Full record

ArticleNucleic acids research2016

Promoter-enhancer looping at the PPARγ2 locus during adipogenic differentiation requires the Prmt5 methyltransferase.

Scott E LeBlanc, Qiong Wu, Pallavi Lamba, Saïd Sif, Anthony N Imbalzano

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

25 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Inhibition of triglyceride metabolism-associated enhancers alters lipid deposition during adipocyte differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. A CCL2Nature communications · 2023
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Epigenetic Regulation of Adipogenesis in Development of Metabolic Syndrome.Frontiers in cell and developmental biology · 2020
    Review
  20. 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

5 authors at 2 institutions in 2 countries.

Scott E LeBlancDepartment of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Qiong WuDepartment of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Pallavi LambaDepartment of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Saïd SifDepartment of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha, Qatar Department of Internal Medicine, The Ohio State University College of Medicine, 395 W. 12th Avenue, Third Floor, Columbus, OH 43210, USA.
Anthony N ImbalzanoDepartment of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Anthony.imbalzano@umassmed.edu.
University of Massachusetts Chan Medical School · USQatar University · QA

Funding

PILOT AND FEASIBILITY PROGRAMP30DK032520 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CZECH, MICHAEL P · 1986 to 2010
$14.6M
TRANSCRIPTION FACTOR FUNCTION IN CHROMATINR01GM056244 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI IMBALZANO, ANTHONY N · 1997 to 2019
$6.7M
Epigenetic Control of AdipogenesisR01DK084278 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI IMBALZANO, ANTHONY N, SIF, SAID · 2009 to 2010
$746k
Control of Adipogenesis by Arginine MethyltransferasesF32DK082263 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LEBLANC, SCOTT E · 2009 to 2012
$159k
NIDDK NIH HHS F32 DK082263NIDDK NIH HHS P30 DK032520NIDDK NIH HHS R01 DK084278NIGMS NIH HHS R01 GM056244
6 · The paper itself

Abstract

PPARγ2 is a critical lineage-determining transcription factor that is essential for adipogenic differentiation. Here we report characterization of the three-dimensional structure of the PPARγ2 locus after the onset of adipogenic differentiation and the mechanisms by which it forms. We identified a differentiation-dependent loop between the PPARγ2 promoter and an enhancer sequence 10 kb upstream that forms at the onset of PPARγ2 expression. The arginine methyltransferase Prmt5 was required for loop formation, and overexpression of Prmt5 resulted in premature loop formation and earlier onset of PPARγ2 expression. Kinetic studies of regulatory factor interactions at the PPARγ2 promoter and enhancer revealed enhanced interaction of Prmt5 with the promoter that preceded stable association of Prmt5 with enhancer sequences. Prmt5 knockdown prevented binding of both MED1, a subunit of Mediator complex that facilitates enhancer-promoter interactions, and Brg1, the ATPase of the mammalian SWI/SNF chromatin remodeling enzyme required for PPARγ2 activation and adipogenic differentiation. The data indicate a dynamic association of Prmt5 with the regulatory sequences of the PPARγ2 gene that facilitates differentiation-dependent, three-dimensional organization of the locus. In addition, other differentiation-specific, long-range chromatin interactions showed Prmt5-dependence, indicating a more general role for Prmt5 in mediating higher-order chromatin connections in differentiating adipocytes.

Indexed as

Cell DifferentiationEnhancer Elements, GeneticGenetic LociPromoter Regions, Genetic3T3-L1 CellsAdipogenesisAnimalsCCAAT-Enhancer-Binding ProteinsCell LineChromatin Assembly and DisassemblyDNA HelicasesGene Expression Regulation, DevelopmentalGene Knockdown TechniquesMediator Complex Subunit 1MiceNuclear ProteinsCCAAT-Enhancer-Binding ProteinsDNA HelicasesMed1 protein, mouseMediator Complex Subunit 1Nuclear ProteinsPPAR gammaPrmt5 protein, mouseProtein-Arginine N-MethyltransferasesSmarca4 protein, mouseTranscription Factors

Identifiers

PMID26935580
PMCPMC4914087
OpenAlexW2293828174

What OpenQuestion holds

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LicenceCC BY-NC
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.