Evidence map›Paper›PMID 25690854›Full record

ArticleNature biotechnology2015

C2H2 zinc finger proteins greatly expand the human regulatory lexicon.

Hamed S Najafabadi, Sanie Mnaimneh, Frank W Schmitges, Michael Garton, Kathy N Lam, Ally Yang, Mihai Albu, Matthew T Weirauch, Ernest Radovani, Philip M Kim and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed, 2 pooled it
17.9field-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

217 citing papers in PubMed, 2 syntheses or guidelines pooled it, 368 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Translational lung cancer research · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

157 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

13 authors at 3 institutions in 2 countries.

Hamed S NajafabadiDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Sanie MnaimnehDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Frank W SchmitgesDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Michael GartonDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Kathy N LamDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Ally YangDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.ORCID 0000000286780946
Mihai AlbuDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Matthew T Weirauch1] Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. [2] Canadian Institutes for Advanced Research, Toronto, Ontario, Canada.
Ernest RadovaniDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Philip M Kim1] Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
Jack Greenblatt1] Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Brendan J Frey1] Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada. [2] Canadian Institutes for Advanced Research, Toronto, Ontario, Canada. [3] Department of Computer Science, University of Toronto, Toronto, Ontario, Canada. [4] Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.
Timothy R Hughes1] Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [3] Canadian Institutes for Advanced Research, Toronto, Ontario, Canada.
University of Toronto · CACanadian Institute for Advanced Research · CACincinnati Children's Hospital Medical Center · US

Funding

Canadian Institutes of Health Research MOP-111007Canadian Institutes of Health Research MOP-272138Canadian Institutes of Health Research MOP-77721
6 · The paper itself

Abstract

Cys2-His2 zinc finger (C2H2-ZF) proteins represent the largest class of putative human transcription factors. However, for most C2H2-ZF proteins it is unknown whether they even bind DNA or, if they do, to which sequences. Here, by combining data from a modified bacterial one-hybrid system with protein-binding microarray and chromatin immunoprecipitation analyses, we show that natural C2H2-ZFs encoded in the human genome bind DNA both in vitro and in vivo, and we infer the DNA recognition code using DNA-binding data for thousands of natural C2H2-ZF domains. In vivo binding data are generally consistent with our recognition code and indicate that C2H2-ZF proteins recognize more motifs than all other human transcription factors combined. We provide direct evidence that most KRAB-containing C2H2-ZF proteins bind specific endogenous retroelements (EREs), ranging from currently active to ancient families. The majority of C2H2-ZF proteins, including KRAB proteins, also show widespread binding to regulatory regions, indicating that the human genome contains an extensive and largely unstudied adaptive C2H2-ZF regulatory network that targets a diverse range of genes and pathways.

Indexed as

Genome, HumanCarrier ProteinsChromatinDNA-Binding ProteinsGene Expression RegulationHumansNuclear ProteinsProtein BindingRegulatory Sequences, Nucleic AcidRepressor ProteinsRetroelementsBCL11A protein, humanCarrier ProteinsChromatinDNA-Binding ProteinsNuclear ProteinsRepressor ProteinsRetroelementsZNF350 protein, human

Identifiers

PMID25690854
OpenAlexW2005530496

What OpenQuestion holds

Textmetadata
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.