Evidence map›Paper›PMID 23861383›Full record

ArticleGenome research2013

Bubble-seq analysis of the human genome reveals distinct chromatin-mediated mechanisms for regulating early- and late-firing origins.

Larry D Mesner, Veena Valsakumar, Marcin Cieslik, Rebecca Pickin, Joyce L Hamlin, Stefan Bekiranov

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
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

63 citing papers in PubMed, 108 citations in OpenAlex.

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  18. Super-resolution microscopy reveals stochastic initiation of replication in Drosophila polytene chromosomes.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2022
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3 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Larry D MesnerDepartment of Biochemistry & Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Veena Valsakumar
Marcin Cieslik
Rebecca Pickin
Joyce L Hamlin
Stefan Bekiranov
University of Virginia · US

Funding

REPLICATION OF MAMMALIAN CHROMOSOMESR01GM026108 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MESNER, LARRY D · 1985 to 2011
$4.9M
NIGMS NIH HHS R01 GM026108NIGMS NIH HHS R01-GM026108
6 · The paper itself

Abstract

We have devised a method for isolating virtually pure and comprehensive libraries of restriction fragments that contained replication initiation sites (bubbles) in vivo. We have now sequenced and mapped the bubble-containing fragments from GM06990, a near-normal EBV-transformed lymphoblastoid cell line, and have compared origin distributions with a comprehensive replication timing study recently published for this cell line. We find that early-firing origins, which represent ∼32% of all origins, overwhelmingly represent zones, associate only marginally with active transcription units, are localized within large domains of open chromatin, and are significantly associated with DNase I hypersensitivity. Origin "density" falls from early- to mid-S-phase, but rises again in late S-phase to levels only 17% lower than in early S-phase. Unexpectedly, late origin density calculated on the 1-Mb scale increases as a function of increasing chromatin compaction. Furthermore, the median efficiency of origins in late-replicating, heterochromatic domains is only 25% lower than in early-replicating euchromatic loci. Thus, the activation of early- and late-firing origins must be regulated by quintessentially different mechanisms. The aggregate data can be unified into a model in which initiation site selection is driven almost entirely by epigenetic factors that fashion both the long-range and local chromatin environments, with underlying DNA sequence and local transcriptional activity playing only minor roles. Importantly, the comprehensive origin map we have prepared for GM06990 overlaps moderately well with origin maps recently reported for the genomes of four different human cell lines based on the distributions of small nascent strands.

Indexed as

Genome, HumanTranscriptional ActivationCell Line, TumorChromatinDeoxyribonuclease IDNA Replication TimingEpigenomicsGenetic LociHeLa CellsHumansModels, GeneticMolecular Sequence DataReplication OriginSequence Analysis, DNATranscription, GeneticChromatinDeoxyribonuclease I

Identifiers

PMID23861383
PMCPMC3814878
OpenAlexW2131775409

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.