Evidence map›Paper›PMID 14673087›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2004

Hairpin-bisulfite PCR: assessing epigenetic methylation patterns on complementary strands of individual DNA molecules.

Charles D Laird, Nicole D Pleasant, Aaron D Clark, Jessica L Sneeden, K M Anwarul Hassan, Nathan C Manley, Jay C Vary, Todd Morgan, R Scott Hansen, Reinhard Stöger

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

100 citing papers in PubMed, 219 citations in OpenAlex.

  1. Article
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  3. SCoTCH-seq reveals that 5-hydroxymethylcytosine encodes regulatory information across DNA strands.Proceedings of the National Academy of Sciences of the United States of America · 2025
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40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Charles D LairdDepartment of Biology, Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA. cdlaird@u.washington.edu
Nicole D Pleasant
Aaron D Clark
Jessica L Sneeden
K M Anwarul Hassan
Nathan C Manley
Jay C Vary
Todd Morgan
R Scott Hansen
Reinhard Stöger
Harvard University · USUniversity of Washington · US

Funding

DOSAGE COMPENSATION IN MAMMALS: X-INACTIVATIONR01HD016659 · NICHD · UNIVERSITY OF WASHINGTON · PI GARTLER, STANLEY · 1996 to 2004
$1.9M
MOLECULAR GENETICS AND EPIGENETICS OF FRAGILE X SYNDROMER01GM053805 · NIGMS · UNIVERSITY OF WASHINGTON · PI LAIRD, CHARLES D · 1995 to 2004
$918k
DOSAGE COMPENSATION IN MAMMALS: X-INACTIVATIONR37HD016659 · NICHD · UNIVERSITY OF WASHINGTON · PI GARTLER, STANLEY · 1986 to 1995
–
NICHD NIH HHS HD16659NICHD NIH HHS R01 HD016659NIGMS NIH HHS GM53805NIGMS NIH HHS GM83805NIGMS NIH HHS R01 GM053805
6 · The paper itself

Abstract

Epigenetic inheritance, the transmission of gene expression states from parent to daughter cells, often involves methylation of DNA. In eukaryotes, cytosine methylation is a frequent component of epigenetic mechanisms. Failure to transmit faithfully a methylated or an unmethylated state of cytosine can lead to altered phenotypes in plants and animals. A central unresolved question in epigenetics concerns the mechanisms by which a locus maintains, or changes, its state of cytosine methylation. We developed "hairpin-bisulfite PCR" to analyze these mechanisms. This method reveals the extent of methylation symmetry between the complementary strands of individual DNA molecules. Using hairpin-bisulfite PCR, we determined the fidelity of methylation transmission in the CpG island of the FMR1 gene in human lymphocytes. For the hypermethylated CpG island of this gene, characteristic of inactive-X alleles, we estimate a maintenance methylation efficiency of approximately 0.96 per site per cell division. For de novo methylation efficiency (E(d)), remarkably different estimates were obtained for the hypermethylated CpG island (E(d) = 0.17), compared with the hypomethylated island on the active-X chromosome (E(d) < 0.01). These results clarify the mechanisms by which the alternative hypomethylated and hypermethylated states of CpG islands are stably maintained through many cell divisions. We also analyzed a region of human L1 transposable elements. These L1 data provide accurate methylation patterns for the complementary strand of each repeat sequence analyzed. Hairpin-bisulfite PCR will be a powerful tool in studying other processes for which genetic or epigenetic information differs on the two complementary strands of DNA.

Indexed as

DNA MethylationRNA-Binding ProteinsAllelesBase SequenceChromosomes, Human, XCpG IslandsCytosineDNADNA Transposable ElementsDosage Compensation, GeneticEpigenesis, GeneticFemaleFragile X Messenger Ribonucleoprotein 1HumansMolecular Sequence DataNerve Tissue ProteinsCytosineDNADNA Transposable ElementsFMR1 protein, humanFragile X Messenger Ribonucleoprotein 1hydrogen sulfiteNerve Tissue ProteinsRNA-Binding ProteinsSulfites

Identifiers

PMID14673087
PMCPMC314163
OpenAlexW2082550660

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.