Evidence map›Paper›PMID 28204611›Full record

ArticleNucleic acids research2017

A genome-integrated massively parallel reporter assay reveals DNA sequence determinants of cis-regulatory activity in neural cells.

Brett B Maricque, Joseph D Dougherty, Barak A Cohen

Abstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
–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

39 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. UnlockingNAR genomics and bioinformatics · 2026
    Article
  3. Article
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  6. Article
  7. Article
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  9. Article
  10. Article
  11. Review
  12. Review
  13. Systematic assays and resources for the functional annotation of non-coding variants.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2022
    Article
  14. Article
  15. Focus on your locus with a massively parallel reporter assay.Journal of neurodevelopmental disorders · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

3 authors.

Brett B Maricque
Joseph D Dougherty
Barak A Cohen

Funding

PROMOTERSR01GM092910 · NIGMS · WASHINGTON UNIVERSITY · PI Barak A Cohen · 2011 to 2026
$6.6M
Translational Neuroscience Training Grant.T32MH015174 · NIMH · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DENNY, CHRISTINE ANN · 1985 to 2020
$4.0M
MASSIVELY PARALLEL CIS-REGULATORY ELEMENT ANALYSIS IN MAMMALIAN CELLSR01HG006790 · NHGRI · WASHINGTON UNIVERSITY · PI COHEN, BARAK A, CORBO, JOSEPH · 2012 to 2014
$1.1M
MASSIVELY PARALLEL CHARACTERIZATION OF CIS-REGULATORY ELEMENTS IN THE BRAINR01HG008687 · NHGRI · WASHINGTON UNIVERSITY · PI COHEN, BARAK A · 2015 to 2017
$1.1M
NHGRI NIH HHS R01 HG006790NHGRI NIH HHS R01 HG008687NIGMS NIH HHS R01 GM092910NIMH NIH HHS T32 MH015174
6 · The paper itself

Abstract

Recent large-scale genomics efforts to characterize the cis-regulatory sequences that orchestrate genome-wide expression patterns have produced impressive catalogues of putative regulatory elements. Most of these sequences have not been functionally tested, and our limited understanding of the non-coding genome prevents us from predicting which sequences are bona fide cis-regulatory elements. Recently, massively parallel reporter assays (MPRAs) have been deployed to measure the activity of putative cis-regulatory sequences in several biological contexts, each with specific advantages and distinct limitations. We developed LV-MPRA, a novel lentiviral-based, massively parallel reporter gene assay, to study the function of genome-integrated regulatory elements in any mammalian cell type; thus, making it possible to apply MPRAs in more biologically relevant contexts. We measured the activity of 2,600 sequences in U87 glioblastoma cells and human neural progenitor cells (hNPCs) and explored how regulatory activity is encoded in DNA sequence. We demonstrate that LV-MPRA can be applied to estimate the effects of local DNA sequence and regional chromatin on regulatory activity. Our data reveal that primary DNA sequence features, such as GC content and dinucleotide composition, accurately distinguish sequences with high activity from sequences with low activity in a full chromosomal context, and may also function in combination with different transcription factor binding sites to determine cell type specificity. We conclude that LV-MPRA will be an important tool for identifying cis-regulatory elements and stimulating new understanding about how the non-coding genome encodes information.

Indexed as

Regulatory Elements, TranscriptionalBinding SitesCell Line, TumorCells, CulturedDNAGene LibraryGenes, ReporterGenome, HumanHumansLentivirusNeural Stem CellsNucleotide MotifsSequence Analysis, DNATranscription FactorsVirus AssemblyDNATranscription Factors

Identifiers

PMID28204611
PMCPMC5389540

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.