Evidence map›Paper›PMID 25972927›Full record

ArticleEpigenetics & chromatin2015

DNase I hypersensitivity analysis of the mouse brain and retina identifies region-specific regulatory elements.

Matthew S Wilken, Joseph A Brzezinski, Anna La Torre, Kyle Siebenthall, Robert Thurman, Peter Sabo, Richard S Sandstrom, Jeff Vierstra, Theresa K Canfield, R Scott Hansen and 3 more

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.3field-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

39 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Pathogenic variants inGenome research · 2024
    Article
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  15. TheProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Article
  17. Article
  18. Mapping theProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  19. Enhancer transcription identifiesDevelopment (Cambridge, England) · 2020
    Article
  20. Epigenetics in neuronal regeneration.Seminars in cell & developmental biology · 2020
    Review
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

13 authors at 3 institutions in 1 country.

Matthew S WilkenDepartment of Biological Structure, University of Washington, 1959 NE Pacific Street, Box 357420, Seattle, WA 98195 USA ; Molecular and Cellular Biology Program, University of Washington, MCB Program Office, T-466 Health Sciences Building, Box 357275, Seattle, WA 98195 USA.
Joseph A BrzezinskiDepartment of Biological Structure, University of Washington, 1959 NE Pacific Street, Box 357420, Seattle, WA 98195 USA ; Department of Ophthalmology, University of Colorado School of Medicine, 1675 Aurora Court, Aurora, CO 80045 USA.
Anna La TorreDepartment of Biological Structure, University of Washington, 1959 NE Pacific Street, Box 357420, Seattle, WA 98195 USA.
Kyle SiebenthallDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Robert ThurmanDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Peter SaboDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Richard S SandstromDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Jeff VierstraDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Theresa K CanfieldDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
R Scott HansenDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Michael A BenderDepartment of Pediatrics, University of Washington, 1959 NE Pacific St, Health Sciences Building, Seattle, WA Box 356320, 98195 USA ; Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109 USA.
John StamatoyannopoulosDepartment of Genome Sciences, University of Washington, Foege Building S-250, 3720 15th Ave NE, Box 355065, Seattle, WA 98195 USA.
Thomas A RehDepartment of Biological Structure, University of Washington, 1959 NE Pacific Street, Box 357420, Seattle, WA 98195 USA.
Seattle University · USUniversity of Washington · USUniversity of Colorado Denver · US

Funding

Vision Research CoreP30EY001730 · NEI · UNIVERSITY OF WASHINGTON · PI JAMES Bryant HURLEY · 1985 to 2026
$23.5M
Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI WARE, CAROL B · 2007 to 2017
$20.6M
A Comprehensive catalog of human DNasel hypersensitive sitesU54HG004592 · NHGRI · UNIVERSITY OF WASHINGTON · PI STAMATOYANNOPOULOS, JOHN A · 2007 to 2011
$15.0M
FUNCTION OF HUMAN &MOUSE B GLOBIN LOCUS CONTROL REGIONSR37DK044746 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1997 to 2016
$12.3M
Environmetal Pathology/Toxicology Training ProgramT32ES007032 · NIEHS · UNIVERSITY OF WASHINGTON · PI FAUSTMAN, ELAINE M, ROSENFELD, MICHAEL E · 1985 to 2023
$10.7M
Supplement to EY021482 to carry out a screen for retinal regeneration using CRISPR-Cas9 gene activation.R01EY021482 · NEI · UNIVERSITY OF WASHINGTON · PI THOMAS A REH · 2011 to 2026
$6.3M
NEI NIH HHS P30 EY001730NEI NIH HHS R01 EY021482NHGRI NIH HHS U54 HG004592NIDDK NIH HHS R37 DK044746NIEHS NIH HHS T32 ES007032NIGMS NIH HHS P01 GM081619
6 · The paper itself

Abstract

backgroundThe brain, spinal cord, and neural retina comprise the central nervous system (CNS) of vertebrates. Understanding the regulatory mechanisms that underlie the enormous cell-type diversity of the CNS is a significant challenge. Whole-genome mapping of DNase I-hypersensitive sites (DHSs) has been used to identify cis-regulatory elements in many tissues. We have applied this approach to the mouse CNS, including developing and mature neural retina, whole brain, and two well-characterized brain regions, the cerebellum and the cerebral cortex.

resultsFor the various regions and developmental stages of the CNS that we analyzed, there were approximately the same number of DHSs; however, there were many DHSs unique to each CNS region and developmental stage. Many of the DHSs are likely to mark enhancers that are specific to the specific CNS region and developmental stage. We validated the DNase I mapping approach for identification of CNS enhancers using the existing VISTA Browser database and with in vivo and in vitro electroporation of the retina. Analysis of transcription factor consensus sites within the DHSs shows distinct region-specific profiles of transcriptional regulators particular to each region. Clustering developmentally dynamic DHSs in the retina revealed enrichment of developmental stage-specific transcriptional regulators. Additionally, we found reporter gene activity in the retina driven from several previously uncharacterized regulatory elements surrounding the neurodevelopmental gene Otx2. Identification of DHSs shared between mouse and human showed region-specific differences in the evolution of cis-regulatory elements.

conclusionsOverall, our results demonstrate the potential of genome-wide DNase I mapping to cis-regulatory questions regarding the regional diversity within the CNS. These data represent an extensive catalogue of potential cis-regulatory elements within the CNS that display region and temporal specificity, as well as a set of DHSs common to CNS tissues. Further examination of evolutionary conservation of DHSs between CNS regions and different species may reveal important cis-regulatory elements in the evolution of the mammalian CNS.

Indexed as

Central nervous systemCis-regulationDNase-seqRetina

Identifiers

PMID25972927
PMCPMC4429822
OpenAlexW2138242641

What OpenQuestion holds

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Registered trials

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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.