Evidence map›Paper›PMID 22955619›Full record

ArticleNature2012

Architecture of the human regulatory network derived from ENCODE data.

Mark B Gerstein, Anshul Kundaje, Manoj Hariharan, Stephen G Landt, Koon-Kiu Yan, Chao Cheng, Xinmeng Jasmine Mu, Ekta Khurana, Joel Rozowsky, Roger Alexander and 46 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 882 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
882citing papers in PubMed, 2 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

882 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  20. Genetics of Sudden Cardiac Death.Diseases (Basel, Switzerland) · 2025
    Review

822 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

56 authors.

Mark B Gerstein *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Anshul Kundaje *Department of Computer Science, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Manoj Hariharan *Department of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Stephen G Landt *Department of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Koon-Kiu Yan *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Chao Cheng *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Xinmeng Jasmine Mu *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Ekta Khurana *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Joel Rozowsky *Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Ave, New Haven, CT 06520, USA.
Roger Alexander *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Renqiang Min *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Pedro Alves *Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Alexej AbyzovProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Nick AddlemanDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Nitin BhardwajProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Alan P BoyleDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Philip CaytingDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Alexandra CharosDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
David Z ChenDepartment of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Ave, New Haven, CT 06520, USA.
Yong ChengDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Declan ClarkeDepartment of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
Catharine EastmanDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Ghia EuskirchenDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Seth FrietzeDepartment of Biochemistry & Molecular Biology, University of Southern California, Norris Comprehensive Cancer Center, 1450 Biggy Street, NRT 6503, Los Angeles, CA 90089, USA.
Yao FuProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Jason GertzHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Fabian GrubertDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Arif HarmanciProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Preti JainHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Maya KasowskiDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Phil LacrouteDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Jing Jane LengProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Jin LianDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Hannah MonahanDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Henriette O'GeenGenome Center, University of California-Davis, 451 Health Sciences Drive, Davis, CA 95616, USA.
Zhengqing OuyangDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
E Christopher PartridgeHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Dorrelyn PatacsilDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Florencia PauliHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Debasish RahaDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Lucia RamirezDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Timothy E ReddyHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Brian ReedDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Minyi ShiDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Teri SliferDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Jing WangProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Linfeng WuDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Xinqiong YangDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.
Kevin Y YipProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Gili Zilberman-SchapiraProgram in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA.
Serafim BatzoglouDepartment of Computer Science, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Arend SidowDepartment of Pathology, Stanford University, SUMC L235 (Edwards Bldg), 300 Pasteur Drive, Stanford, CA 94305, USA.
Peggy J FarnhamDepartment of Biochemistry & Molecular Biology, University of Southern California, Norris Comprehensive Cancer Center, 1450 Biggy Street, NRT 6503, Los Angeles, CA 90089, USA.
Richard M MyersHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Sherman M WeissmanDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Michael SnyderDepartment of Genetics, Stanford University, 300 Pasteur Dr., M-344 Stanford, CA 94305, USA.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Production Center for Global Mapping of Regulatory ElementsU54HG004558 · NHGRI · YALE UNIVERSITY · PI SNYDER, MICHAEL P. · 2007 to 2011
$15.4M
PREDOCTORAL PROGRAM IN BIOPHYSICST32GM008283 · NIGMS · YALE UNIVERSITY · PI XIONG, YONG · 1988 to 2022
$10.5M
EDAC: ENCODE Data Analysis CenterU01HG004695 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI BIRNEY, EWAN · 2008 to 2012
$6.4M
NHGRI NIH HHS U01 HG004695NHGRI NIH HHS U54 HG004558NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM008283NIGMS NIH HHS T32GM008283-24
6 · The paper itself

Abstract

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

Indexed as

Encyclopedias as TopicMolecular Sequence AnnotationAllelesCell LineDNAGATA1 Transcription FactorGene Expression ProfilingGene Regulatory NetworksGenome, HumanGenomicsHumansK562 CellsOrgan SpecificityPhosphorylationPolymorphism, Single NucleotideProtein Interaction MapsDNAGATA1 Transcription FactorRNA, UntranslatedTranscription Factors

Identifiers

PMID22955619
PMCPMC4154057

What OpenQuestion holds

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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.