Evidence map›Paper›PMID 26225157›Full record

ArticleClinical epigenetics2015

Global DNA methylation changes and differential gene expression in Anaplasma phagocytophilum-infected human neutrophils.

Sara H G Sinclair, Srinivasan Yegnasubramanian, J Stephen Dumler

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
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  5. Review
  6. Article
  7. Article
  8. Article
  9. Frontiers in cellular and infection microbiology · 2022
    Article
  10. Article
  11. Article
  12. Review
  13. Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Gene activation precedes DNA demethylation in response to infection in human dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  20. Article
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

3 authors at 2 institutions in 1 country.

Sara H G SinclairGraduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD USA ; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD USA ; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD USA ; Department of Microbiology and Immunology, University School of Medicine, Baltimore, MD USA.
Srinivasan YegnasubramanianSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD USA.
J Stephen DumlerGraduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD USA ; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD USA ; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD USA ; Department of Microbiology and Immunology, University School of Medicine, Baltimore, MD USA.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
EHRLICHIA-GRANULOCYTE INTERACTIONS AND INFECTIONR01AI044102 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI DUMLER, JOHN STEPHEN · 2000 to 2019
$5.3M
NCI NIH HHS P30 CA006973NIAID NIH HHS R01 AI044102
6 · The paper itself

Abstract

backgroundAnaplasma phagocytophilum is an obligate intracellular prokaryotic pathogen that both infects and replicates within human neutrophils. The bacterium represses multiple antimicrobial functions while simultaneously increasing proinflammatory functions by reprogramming the neutrophil genome. Previous reports show that many observed phenotypic changes are in part explained by altered gene transcription. We recently identified that large chromosomal regions of the neutrophil genome are differentially expressed during A. phagocytophilum infection. Because of this, we sought to determine whether gene expression programs altered by infection were the result of changes in the host neutrophil DNA methylome.

resultsWithin 24 h of infection, marked increases in DNA methylation were observed genome-wide as compared with mock-infected controls and pharmacologic inhibition of DNA methyltransferases resulted in decreased bacterial growth. New regions of DNA methylation were enriched at intron and exon junctions; however, intragenic methylation did not correlate with altered gene expression. In contrast, intergenic DNA methylation was associated with A. phagocytophilum-induced gene expression changes. Within the major histocompatibility complex locus on chromosome 6, a region with marked changes in infection-induced differential gene expression, new regions of methylation were localized to boundaries of active and inactive chromatin.

conclusionsThese data strongly suggest that A. phagocytophilum infection, in addition to altering histone structure, alters DNA methylation and the epigenome of its host cell to promote survival and replication, providing evidence that such bacterial infection can radically alter the epigenome of its host cell.

Indexed as

Anaplasma phagocytophilumCellular reprogrammingDNA methylationHypermethylationMHC locus

Identifiers

PMID26225157
PMCPMC4518890
OpenAlexW1769320112

What OpenQuestion holds

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LicenceCC BY
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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.