Evidence map›Paper›PMID 25079558›Full record

ArticleNature2014

DNA methylation dynamics of the human preimplantation embryo.

Zachary D Smith, Michelle M Chan, Kathryn C Humm, Rahul Karnik, Shila Mekhoubad, Aviv Regev, Kevin Eggan, Alexander Meissner

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

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 320 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
320citing papers in PubMed, 1 pooled it
31.7field-weighted citation impact, top 1% 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

320 citing papers in PubMed, 1 synthesis or guideline pooled it, 582 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026
    Review
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  5. Embracing non-linearity in human ageing.Nature reviews. Genetics · 2026
    Review
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Exit from totipotency in mammals: an epigenetic perspective.Frontiers in cell and developmental biology · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

260 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Zachary D Smith1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5].
Michelle M Chan1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3].
Kathryn C Humm1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Division of Reproductive Endocrinology &Infertility, Department of Obstetrics &Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [3] Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02215, USA [4] Boston IVF, Waltham, Massachusetts 02451, USA [5] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [6].
Rahul Karnik1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Shila Mekhoubad1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Aviv Regev1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Kevin Eggan1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Alexander Meissner1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Broad Institute · USHarvard Stem Cell Institute · USHarvard University · US

Funding

Regulatory Roles and Dynamics of Nuclear long-noncoding RNAs in PluripotencyP01GM099117 · NIGMS · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2011 to 2021
$21.2M
Center for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6M
Production sequencing of reference human epigenomesU01ES017155 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN, MEISSNER, ALEXANDER · 2008 to 2012
$15.4M
The temporal reconfiguration of regulatory networks: From yeast to cancerDP1OD003958 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI REGEV, AVIV · 2008 to 2011
$3.3M
Howard Hughes Medical InstituteNHGRI NIH HHS 1P50HG006193-01NHGRI NIH HHS P50 HG006193NIEHS NIH HHS U01 ES017155NIGMS NIH HHS P01 GM099117NIGMS NIH HHS P01GM099117NIH HHS 5DP1OD003958NIH HHS DP1 OD003958
6 · The paper itself

Abstract

In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell-type-specific regulation directed by DNA binding factors. This comparatively static landscape is in marked contrast with the events of fertilization, during which the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, although methylation remains detectable at several notable features. These dynamics have been extensively characterized in the mouse, with only limited observations available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies. Although most features share similar dynamics to those in mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island promoters that extend beyond known imprint control regions. Retrotransposon regulation is also highly diverse, and transitions from maternally to embryonically expressed elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation.

Indexed as

DNA MethylationAnimalsBlastocystCell LineCpG IslandsDNAEmbryonic Stem CellsFemaleGene Expression Regulation, DevelopmentalHumansMaleMiceMice, Inbred C57BLDNA

Identifiers

PMID25079558
PMCPMC4178976
OpenAlexW2107202213

What OpenQuestion holds

Textmetadata
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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.