Evidence map›Paper›PMID 26308346›Full record

ArticlePloS one2015

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact.

Puya G Yazdi, Brian A Pedersen, Jared F Taylor, Omar S Khattab, Yu-Han Chen, Yumay Chen, Steven E Jacobsen, Ping H Wang

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  10. Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  11. Article
  12. Nonmutational mechanism of inheritance in the ArchaeonProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  13. Article
  14. Evolution of Local Mutation Rate and Its Determinants.Molecular biology and evolution · 2017
    Article
  15. Review
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  17. 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

8 authors at 2 institutions in 1 country.

Puya G YazdiUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America; Department of Medicine, University of California at Irvine, Irvine, California, United States of America.
Brian A PedersenUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America; Department of Medicine, University of California at Irvine, Irvine, California, United States of America.
Jared F TaylorUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America; Department of Medicine, University of California at Irvine, Irvine, California, United States of America.
Omar S KhattabUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America.
Yu-Han ChenUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America; Department of Medicine, University of California at Irvine, Irvine, California, United States of America.
Yumay ChenUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America; Department of Medicine, University of California at Irvine, Irvine, California, United States of America.
Steven E JacobsenDepartment of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California, United States of America; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, California, United States of America; Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, California, United States of America.
Ping H WangUC Irvine Diabetes Center, University of California at Irvine, Irvine, California, United States of America; Sue and Bill Gross Stem Cell Research Center, University of California at Irvine, Irvine, California, United States of America; Department of Medicine, University of California at Irvine, Irvine, California, United States of America; Department of Biological Chemistry, University of California at Irvine, Irvine, California, United States of America; Department of Physiology & Biophysics, University of California at Irvine, Irvine, California, United States of America.
University of California, Irvine · USUniversity of California, Los Angeles · US

Funding

University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001414
6 · The paper itself

Abstract

Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer.

Indexed as

Genome, HumanCells, CulturedChromatinDNADNA RepairEmbryonic Stem CellsGenomicsHistonesHumansMutation RateNeoplasmsNucleosomesPromoter Regions, GeneticChromatinDNAHistonesNucleosomes

Identifiers

PMID26308346
PMCPMC4550472
OpenAlexW1704735416

What OpenQuestion holds

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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.