Evidence map›Paper›PMID 35315433›Full record

ArticleNature communications2022

Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation.

Anat Kreimer, Tal Ashuach, Fumitaka Inoue, Alex Khodaverdian, Chengyu Deng, Nir Yosef, Nadav Ahituv

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. A massively parallel reporter assay ofbioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Just a SNP away: The future ofCell insight · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. Article
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

7 authors.

Anat Kreimer *Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA. kreimer@cabm.rutgers.edu.
Tal Ashuach *Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, CA, 94720, USA.
Fumitaka Inoue *Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-0657-434X
Alex KhodaverdianDepartment of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, CA, 94720, USA.
Chengyu DengDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
Nir YosefDepartment of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, CA, 94720, USA. niryosef@berkeley.edu.ORCID http://orcid.org/0000-0001-9004-1225
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA. nadav.ahituv@ucsf.edu.ORCID http://orcid.org/0000-0002-7434-8144

Funding

GENOMICST32HG000047 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI RASMUS NIELSEN, Daniel Soleyman Rokhsar · 2000 to 2026
$13.5M
Massively parallel characterization of variants and elements impacting transcriptional regulation in dynamic cellular systemsUM1HG011966 · NHGRI · UNIVERSITY OF WASHINGTON · PI Nadav Ahituv, Jay Ashok Shendure · 2021 to 2026
$9.7M
Massively parallel reporter assays and genome editing of ENCODE predicted regulatory elementsUM1HG009408 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, SHENDURE, JAY ASHOK · 2017 to 2021
$7.6M
Multiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0M
Massively parallel dissection of psychiatric regulatory networksR01MH109907 · NIMH · J. DAVID GLADSTONE INSTITUTES · PI AHITUV, NADAV, POLLARD, KATHERINE S. · 2016 to 2020
$3.4M
Massively parallel characterization of psychiatric disease associated regulatory elements in defined cell typesU01MH116438 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, POLLARD, KATHERINE S. · 2018 to 2021
$2.7M
Rarely Common: Uncovering the dominant role of rare variants in the genetic architecture of complex human traits.R01GM142112 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2021 to 2024
$2.2M
Early Epigenetic Footprint of Neurological DiseasesR00MH117393 · NIMH · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI KREIMER, ANAT · 2020 to 2022
$747k
Massively parallel characterization of psychiatric disease associated regulatory elements in defined cell typesR01MH116438 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, POLLARD, KATHERINE S. · 2022 to 2022
$668k
Acquisition of Covaris E220 and Sciclone G3 systems for high throughput sequencinS10OD010786 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI COMAI, LUCA · 2012 to 2012
$311k
Early epigenetic footprint of neurological diseasesK99MH117393 · NIMH · UNIVERSITY OF CALIFORNIA BERKELEY · PI KREIMER, ANAT · 2018 to 2019
$231k
NHGRI NIH HHS T32 HG000047NHGRI NIH HHS UM1 HG009408NHGRI NIH HHS UM1 HG011966NIGMS NIH HHS R01 GM142112NIH HHS S10 OD010786NIMH NIH HHS K99 MH117393NIMH NIH HHS R00 MH117393NIMH NIH HHS R01 MH109907NIMH NIH HHS R01 MH116438NIMH NIH HHS R01 MH125246NIMH NIH HHS U01 MH116438
6 · The paper itself

Abstract

Gene regulatory elements play a key role in orchestrating gene expression during cellular differentiation, but what determines their function over time remains largely unknown. Here, we perform perturbation-based massively parallel reporter assays at seven early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide cellular differentiation. By perturbing over 2,000 putative DNA binding motifs in active regulatory regions, we delineate four categories of functional elements, and observe that activity direction is mostly determined by the sequence itself, while the magnitude of effect depends on the cellular environment. We also find that fine-tuning transcription rates is often achieved by a combined activity of adjacent activating and repressing elements. Our work provides a blueprint for the sequence components needed to induce different transcriptional patterns in general and specifically during neural differentiation.

Indexed as

Biological AssayRegulatory Sequences, Nucleic Acid

Identifiers

PMID35315433
PMCPMC8938438

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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.