Evidence map›Paper›PMID 22684627›Full record

ArticleNucleic acids research2012

Integrated genome analysis suggests that most conserved non-coding sequences are regulatory factor binding sites.

Martin Hemberg, Jesse M Gray, Nicole Cloonan, Scott Kuersten, Sean Grimmond, Michael E Greenberg, Gabriel Kreiman

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Roles of noncoding RNAs in preeclampsia.Reproductive biology and endocrinology : RB&E · 2021
    Review
  11. Article
  12. Open medicine (Warsaw, Poland) · 2021
    Article
  13. Regulation of Hippo, TGFβ/SMAD, Wnt/Frontiers in oncology · 2021
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Genomic Views of Transcriptional Enhancers: Essential Determinants of Cellular Identity and Activity-Dependent Responses in the CNS.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
    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

7 authors at 2 institutions in 2 countries.

Martin HembergDepartment of Ophthalmology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02215, USA. martin.hemberg@childrens.harvard.edu
Jesse M Gray
Nicole Cloonan
Scott Kuersten
Sean Grimmond
Michael E Greenberg
Gabriel Kreiman
Harvard University · USUniversity of Queensland · AU

Funding

ELECTRICAL STIMULATION OF IMMEDIATE EARLY GENESR37NS028829 · NINDS · HARVARD MEDICAL SCHOOL · PI GREENBERG, MICHAEL ELDON · 1999 to 2019
$7.4M
ELECTRICAL STIMULATION OF IMMEDIATE GENESR01NS028829 · NINDS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GREENBERG, MICHAEL ELDON · 1990 to 2024
$6.2M
Towards the neuronal correlates of visual awarenessDP2OD006461 · OD · BOSTON CHILDREN'S HOSPITAL · PI KREIMAN, GABRIEL · 2009 to 2009
$2.6M
Interictal discharge events: from physiological effects to cognitive consequencesR21NS070250 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI KREIMAN, GABRIEL · 2011 to 2012
$459k
NIH HHS 1DP2OD006461-01NINDS NIH HHS 1R21NS070250-01A1NINDS NIH HHS NS028829
6 · The paper itself

Abstract

More than 98% of a typical vertebrate genome does not code for proteins. Although non-coding regions are sprinkled with short (<200 bp) islands of evolutionarily conserved sequences, the function of most of these unannotated conserved islands remains unknown. One possibility is that unannotated conserved islands could encode non-coding RNAs (ncRNAs); alternatively, unannotated conserved islands could serve as promoter-distal regulatory factor binding sites (RFBSs) like enhancers. Here we assess these possibilities by comparing unannotated conserved islands in the human and mouse genomes to transcribed regions and to RFBSs, relying on a detailed case study of one human and one mouse cell type. We define transcribed regions by applying a novel transcript-calling algorithm to RNA-Seq data obtained from total cellular RNA, and we define RFBSs using ChIP-Seq and DNAse-hypersensitivity assays. We find that unannotated conserved islands are four times more likely to coincide with RFBSs than with unannotated ncRNAs. Thousands of conserved RFBSs can be categorized as insulators based on the presence of CTCF or as enhancers based on the presence of p300/CBP and H3K4me1. While many unannotated conserved RFBSs are transcriptionally active to some extent, the transcripts produced tend to be unspliced, non-polyadenylated and expressed at levels 10 to 100-fold lower than annotated coding or ncRNAs. Extending these findings across multiple cell types and tissues, we propose that most conserved non-coding genomic DNA in vertebrate genomes corresponds to promoter-distal regulatory elements.

Indexed as

Conserved SequenceRegulatory Elements, TranscriptionalAnimalsBase SequenceBinding SitesDNAGenomeHeLa CellsHumansMicePromoter Regions, GeneticRNA, UntranslatedTranscription, GeneticDNARNA, Untranslated

Identifiers

PMID22684627
PMCPMC3439890
OpenAlexW2151370251

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.