Evidence map›Paper›PMID 24658141›Full record

ArticleNature methods2014

Function-based identification of mammalian enhancers using site-specific integration.

Diane E Dickel, Yiwen Zhu, Alex S Nord, John N Wylie, Jennifer A Akiyama, Veena Afzal, Ingrid Plajzer-Frick, Aileen Kirkpatrick, Berthold Göttgens, Benoit G Bruneau and 2 more

Abstract read
In one paragraph

Article in Nature methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing 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

50 citing papers in PubMed.

  1. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
    Review
  2. Article
  3. Crosstalk BetweenCancers · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Cis-Regulatory Elements in Mammals.International journal of molecular sciences · 2023
    Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Enhancer-gene specificity in development and disease.Development (Cambridge, England) · 2022
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Diane E DickelGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Yiwen ZhuGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Alex S NordGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
John N Wylie1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Roddenberry Center for Stem Cell Biology and Medicine at Gladstone Institutes, San Francisco, California, USA.
Jennifer A AkiyamaGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Veena AfzalGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Ingrid Plajzer-FrickGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Aileen Kirkpatrick1] Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. [2] Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Berthold Göttgens1] Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. [2] Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000000163025705
Benoit G Bruneau1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Roddenberry Center for Stem Cell Biology and Medicine at Gladstone Institutes, San Francisco, California, USA. [3] Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA. [4] Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
Axel Visel1] Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA. [2] US Department of Energy Joint Genome Institute, Walnut Creek, California, USA. [3] School of Natural Sciences, University of California, Merced, Merced, California, USA.
Len A Pennacchio1] Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA. [2] US Department of Energy Joint Genome Institute, Walnut Creek, California, USA.

Funding

NHLBI Pediatric Translational Consortium Administrative Coordinating CenterU01HL098188 · NHLBI · NEW ENGLAND RESEARCH INSTITUTES, INC. · PI HAMZA, TAYE, MILLER, JULIE ELAINE · 2009 to 2015
$41.3M
Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetR01HG003988 · NHGRI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Len Alexander Pennacchio · 2006 to 2026
$24.1M
Center for Mammalian Regulatory GenomicsU54HG006997 · NHGRI · LUDWIG INSTITUTE FOR CANCER RES LTD · PI REN, BING · 2012 to 2016
$14.3M
The Epigenetic Landscape of Heart DevelopmentU01HL098179 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BOYER, LAURIE A, BRUNEAU, BENOIT GAETAN · 2009 to 2014
$10.0M
Genomic, Transgenic and Knockout Resources for Craniofacial Enhancer StudiesU01DE024427 · NIDCR · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI VISEL, AXEL · 2014 to 2018
$3.7M
Research Project: Genome-Wide Atlas of Craniofacial Transcriptional EnhancersU01DE020060 · NIDCR · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI VISEL, AXEL · 2009 to 2013
$2.1M
Genetic and Molecular Approaches To Cardiovascular DiseaseT32HL098057 · NHLBI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI KRAUSS, RONALD M · 2009 to 2013
$1.0M
Developmental and evolutionary dynamics of tissue-specific mammalian enhancers.F32GM105202 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI NORD, ALEXANDER · 2013 to 2014
$60k
Biotechnology and Biological Sciences Research CouncilCancer Research UK 12765Medical Research Council G0900729/1Medical Research Council MC_PC_12009National Centre for the Replacement, Refinement and Reduction of Animals in Research G0900729/1NHGRI NIH HHS R01 HG003988NHGRI NIH HHS R01HG003988NHGRI NIH HHS U54 HG006997NHGRI NIH HHS U54HG006997NHLBI NIH HHS 5T32HL098057NHLBI NIH HHS T32 HL098057NHLBI NIH HHS U01 HL098179NHLBI NIH HHS U01HL098179NHLBI NIH HHS U01 HL098188NIDCR NIH HHS U01 DE020060NIDCR NIH HHS U01DE020060NIDCR NIH HHS U01 DE024427NIGMS NIH HHS F32 GM105202Wellcome Trust
6 · The paper itself

Abstract

The accurate and comprehensive identification of functional regulatory sequences in mammalian genomes remains a major challenge. Here we describe site-specific integration fluorescence-activated cell sorting followed by sequencing (SIF-seq), an unbiased, medium-throughput functional assay for the discovery of distant-acting enhancers. Targeted single-copy genomic integration into pluripotent cells, reporter assays and flow cytometry are coupled with high-throughput DNA sequencing to enable parallel screening of large numbers of DNA sequences. By functionally interrogating >500 kilobases (kb) of mouse and human sequence in mouse embryonic stem cells for enhancer activity we identified enhancers at pluripotency loci including NANOG. In in vitro-differentiated cardiomyocytes and neural progenitor cells, we identified cardiac enhancers and neuronal enhancers, respectively. SIF-seq is a powerful and flexible method for de novo functional identification of mammalian enhancers in a potentially wide variety of cell types.

Indexed as

Enhancer Elements, GeneticAnimalsCell DifferentiationCell SeparationChromosomes, Artificial, BacterialEmbryonic Stem CellsFlow CytometryGene Expression RegulationGene LibraryGenes, ReporterGenetic VectorsGenomicsHigh-Throughput Nucleotide SequencingHumansMiceMice, Transgenic

Identifiers

PMID24658141
PMCPMC4008384

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.