Evidence map›Paper›PMID 36418052›Full record

ArticleGenes & development2022

Oct4:Sox2 binding is essential for establishing but not maintaining active and silent states of dynamically regulated genes in pluripotent cells.

Jerry Hung-Hao Lo, Miguel Edwards, Justin Langerman, Rupa Sridharan, Kathrin Plath, Stephen T Smale

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. OCT4 and Nestin Expression in the Microenvironment of Primary Central Nervous System Lymphomas.International journal of hematology-oncology and stem cell research · 2025
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Expression ofFrontiers in oncology · 2023
    Article
  12. Review
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

6 authors at 2 institutions in 1 country.

Jerry Hung-Hao LoMolecular Biology Institute, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA.
Miguel EdwardsMolecular Biology Institute, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA.
Justin LangermanMolecular Biology Institute, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA.
Rupa SridharanWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA.
Kathrin PlathMolecular Biology Institute, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA.ORCID 0000-0001-7796-3372
Stephen T SmaleMolecular Biology Institute, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA.ORCID 0000-0002-9835-6907
University of California, Los Angeles · USUniversity of Wisconsin–Madison · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Roles of sumoylation and alternative polyadenylation in cellular reprogrammingP01GM099134 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PLATH, KATHRIN · 2011 to 2021
$20.3M
R01 Renewal: Collaboration of chromatin remodeling and signaling pathways in pluripotencyR01GM113033 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SRIDHARAN, RUPA · 2015 to 2023
$2.9M
Selective Regulation of Pro-Inflammatory Genes in MacrophagesR01GM086372 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALE, STEPHEN T · 2008 to 2015
$2.5M
NCI NIH HHS P30 CA016042NIGMS NIH HHS P01 GM099134NIGMS NIH HHS R01 GM086372NIGMS NIH HHS R01 GM113033NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

Much has been learned about the mechanisms of action of pluripotency factors Oct4 and Sox2. However, as with other regulators of cell identity, little is known about the impact of disrupting their binding motifs in a native environment or the characteristics of genes they regulate. By quantitatively examining dynamic ranges of gene expression instead of focusing on conventional measures of differential expression, we found that Oct4 and Sox2 enhancer binding is strongly enriched near genes subject to large dynamic ranges of expression among cell types, with binding sites near these genes usually within superenhancers. Mutagenesis of representative Oct4:Sox2 motifs near such active, dynamically regulated genes revealed critical roles in transcriptional activation during reprogramming, with more limited roles in transcriptional maintenance in the pluripotent state. Furthermore, representative motifs near silent genes were critical for establishing but not maintaining the fully silent state, while genes whose transcript levels varied by smaller magnitudes among cell types were unaffected by nearby Oct4:Sox2 motifs. These results suggest that Oct4 and Sox2 directly establish both active and silent transcriptional states in pluripotent cells at a large number of genes subject to dynamic regulation during mammalian development, but are less important than expected for maintaining transcriptional states.

Indexed as

LearningMammalsAnimalsBinding SitesMutagenesisTranscriptional Activationdifferentiationembryonic stem cellsOct4pluripotencySox2transcription

Identifiers

PMID36418052
PMCPMC9744233
OpenAlexW4309796910

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.