Evidence map›Paper›PMID 23459939›Full record

ArticleMolecular and cellular biology2013

Developmentally programmed 3' CpG island methylation confers tissue- and cell-type-specific transcriptional activation.

Da-Hai Yu, Carol Ware, Robert A Waterland, Jiexin Zhang, Miao-Hsueh Chen, Manasi Gadkari, Govindarajan Kunde-Ramamoorthy, Lagina M Nosavanh, Lanlan Shen

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Oncotarget · 2020
    Article
  6. Article
  7. Epigenetics and Female Reproductive Aging.Frontiers in endocrinology · 2019
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
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  17. Article
  18. Review
  19. Article
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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

9 authors at 3 institutions in 1 country.

Da-Hai YuDepartment of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA.
Carol Ware
Robert A Waterland
Jiexin Zhang
Miao-Hsueh Chen
Manasi Gadkari
Govindarajan Kunde-Ramamoorthy
Lagina M Nosavanh
Lanlan Shen
Children's Nutrition Research Center at Baylor College of Medicine · USThe University of Texas MD Anderson Cancer Center · USUniversity of Washington · US

Funding

Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI REH, THOMAS A · 2007 to 2017
$20.6M
Epigenetic Mechanisms in ObesityR01DK081557 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI WATERLAND, ROBERT A · 2008 to 2012
$1.5M
NIDDK NIH HHS 1R01DK081557NIDDK NIH HHS R01 DK081557NIGMS NIH HHS P01 GM081619NIGMS NIH HHS P01GM081619-01
6 · The paper itself

Abstract

During development, a small but significant number of CpG islands (CGIs) become methylated. The timing of developmentally programmed CGI methylation and associated mechanisms of transcriptional regulation during cellular differentiation, however, remain poorly characterized. Here, we used genome-wide DNA methylation microarrays to identify epigenetic changes during human embryonic stem cell (hESC) differentiation. We discovered a group of CGIs associated with developmental genes that gain methylation after hESCs differentiate. Conversely, erasure of methylation was observed at the identified CGIs during subsequent reprogramming to induced pluripotent stem cells (iPSCs), further supporting a functional role for the CGI methylation. Both global gene expression profiling and quantitative reverse transcription-PCR (RT-PCR) validation indicated opposing effects of CGI methylation in transcriptional regulation during differentiation, with promoter CGI methylation repressing and 3' CGI methylation activating transcription. By studying diverse human tissues and mouse models, we further confirmed that developmentally programmed 3' CGI methylation confers tissue- and cell-type-specific gene activation in vivo. Importantly, luciferase reporter assays provided evidence that 3' CGI methylation regulates transcriptional activation via a CTCF-dependent enhancer-blocking mechanism. These findings expand the classic view of mammalian CGI methylation as a mechanism for transcriptional silencing and indicate a functional role for 3' CGI methylation in developmental gene regulation.

Indexed as

CpG IslandsDNA MethylationGene Expression Regulation, DevelopmentalTranscriptional ActivationAnimalsCCCTC-Binding FactorCell DifferentiationCell LineDNAEmbryonic Stem CellsEpigenesis, GeneticHumansInduced Pluripotent Stem CellsMethylationMiceMice, Inbred C57BLCCCTC-Binding FactorCTCF protein, humanCtcf protein, mouseDNARepressor Proteins

Identifiers

PMID23459939
PMCPMC3624169
OpenAlexW1976095508

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.