Evidence map›Paper›PMID 23892608›Full record

ArticleNature genetics2013

Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model.

Robin P Smith, Leila Taher, Rupali P Patwardhan, Mee J Kim, Fumitaka Inoue, Jay Shendure, Ivan Ovcharenko, Nadav Ahituv

Abstract read
In one paragraph

Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 2 pooled it
10.0field-weighted citation impact, top 1% 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

162 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
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  6. Article
  7. PoolParty: streamlined design of DNA sequence libraries in Python.bioRxiv : the preprint server for biology · 2026
    Article
  8. Transcription factors Lef1 and Rest stimulate recovery from depressive states.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
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  10. Review
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102 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

8 authors at 3 institutions in 2 countries.

Robin P Smith *Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Leila Taher *Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, US National Institutes of Health, Bethesda, Maryland, USA.
Rupali P PatwardhanDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Mee J KimDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Fumitaka InoueDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Ivan OvcharenkoComputational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, US National Institutes of Health, Bethesda, Maryland, USA.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USNational Institutes of Health · USUniversity of Washington · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7M
PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Regulatory landscape of the human genome: comparative and evolutionary analysis.ZIALM200881 · NLM · NATIONAL LIBRARY OF MEDICINE · PI OVCHARENKO, IVAN · 2009 to 2025
$20.1M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YEE, SOOK WAH · 2010 to 2014
$16.3M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
Characterization of regulatory elements leading to human limb malformationsR01HD059862 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, BEJERANO, GILL · 2009 to 2013
$2.2M
Massively parallel, in vivo functional testing of regulatory elementsR01HG006768 · NHGRI · UNIVERSITY OF WASHINGTON · PI AHITUV, NADAV, SHENDURE, JAY ASHOK · 2012 to 2014
$1.8M
Computational & Functional Annotation of the Zebrafish Genome Regulatory ToolboxR01HG005058 · NHGRI · STANFORD UNIVERSITY · PI AHITUV, NADAV, BEJERANO, GILL · 2009 to 2012
$1.6M
Identification & functional characterization of SIM1 obesity-associated variantsR01DK090382 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, VAISSE, CHRISTIAN · 2012 to 2015
$1.3M
Characterization of neuronal gene regulatory elements associated with epilepsyR01NS079231 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV · 2012 to 2015
$1.2M
CIHRIntramural NIH HHSNHGRI NIH HHS 1R01HG006768NHGRI NIH HHS R01 HG005058NHGRI NIH HHS R01HG005058NHGRI NIH HHS R01 HG006768NICHD NIH HHS R01 HD059862NICHD NIH HHS R01HD059862NIDDK NIH HHS 1R01DK090382NIDDK NIH HHS P30 DK026743NIDDK NIH HHS R01 DK090382NIGMS NIH HHS GM61390NIGMS NIH HHS T32 GM007175NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390NINDS NIH HHS 1R01NS079231NINDS NIH HHS R01 NS079231
6 · The paper itself

Abstract

Despite continual progress in the cataloging of vertebrate regulatory elements, little is known about their organization and regulatory architecture. Here we describe a massively parallel experiment to systematically test the impact of copy number, spacing, combination and order of transcription factor binding sites on gene expression. A complex library of ∼5,000 synthetic regulatory elements containing patterns from 12 liver-specific transcription factor binding sites was assayed in mice and in HepG2 cells. We find that certain transcription factors act as direct drivers of gene expression in homotypic clusters of binding sites, independent of spacing between sites, whereas others function only synergistically. Heterotypic enhancers are stronger than their homotypic analogs and favor specific transcription factor binding site combinations, mimicking putative native enhancers. Exhaustive testing of binding site permutations suggests that there is flexibility in binding site order. Our findings provide quantitative support for a flexible model of regulatory element activity and suggest a framework for the design of synthetic tissue-specific enhancers.

Indexed as

Gene Expression RegulationModels, BiologicalRegulatory Sequences, Nucleic AcidAnimalsBinding SitesCell LineCluster AnalysisEnhancer Elements, GeneticGene AmplificationGene DosageGene ExpressionGenes, ReporterHumansLiverMaleMiceTranscription Factors

Identifiers

PMID23892608
PMCPMC3775494
OpenAlexW2008047506

What OpenQuestion holds

Textmetadata
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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.