Evidence map›Paper›PMID 25564442›Full record

ArticleThe EMBO journal2015

Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.

Tõnis Org, Dan Duan, Roberto Ferrari, Amelie Montel-Hagen, Ben Van Handel, Marc A Kerényi, Rajkumar Sasidharan, Liudmilla Rubbi, Yuko Fujiwara, Matteo Pellegrini and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

48 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Transcription Factor TAL1 in Erythropoiesis.Advances in experimental medicine and biology · 2024
    Review
  3. Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Review
  4. Article
  5. Sensitive cluster-free differential expression testing.bioRxiv : the preprint server for biology · 2023
    Article
  6. Article
  7. LMO2 expression is frequent in T-lymphoblastic leukemia and correlates with survival, regardless of T-cell stage.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Advancing Stem Cell Research through Multimodal Single-Cell Analysis.Cold Spring Harbor perspectives in biology · 2020
    Review
  17. Article
  18. Review
  19. Enhancers and MYC interplay in hematopoiesis.Journal of molecular medicine (Berlin, Germany) · 2020
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 1 country.

Tõnis OrgDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Dan DuanDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Roberto FerrariDepartment of Biological Chemistry, University of California, Los Angeles, CA, USA Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA, USA.
Amelie Montel-HagenDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Ben Van HandelDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Marc A KerényiDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Children's Hospital Boston, Howard Hughes Medical Institute Harvard Stem Cell Institute Harvard Medical School, Boston, MA, USA.
Rajkumar SasidharanDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Liudmilla RubbiDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Yuko FujiwaraDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Children's Hospital Boston, Howard Hughes Medical Institute Harvard Stem Cell Institute Harvard Medical School, Boston, MA, USA.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Stuart H OrkinDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Children's Hospital Boston, Howard Hughes Medical Institute Harvard Stem Cell Institute Harvard Medical School, Boston, MA, USA.
Siavash K KurdistaniDepartment of Biological Chemistry, University of California, Los Angeles, CA, USA Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA, USA.
Hanna Ka MikkolaDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA, USA hmikkola@mcdb.ucla.edu.
University of California, Los Angeles · USBroad Center · USHarvard Stem Cell Institute · USHarvard University · USHoward Hughes Medical Institute · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
CORE--ZEBRAFISHP30DK049216 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1999 to 2015
$14.3M
MOLECULAR ANALYSIS OF NORMAL AND TYHALASSEMIC DNAR01HL032259 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1985 to 2022
$8.8M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
NCI NIH HHS P30 CA016042NHLBI NIH HHS R01 HL032259NHLBI NIH HHS T32 HL069766NHLBI NIH HHS T32 HL69766NIDDK NIH HHS P30 DK049216NIDDK NIH HHS P30DK049216
6 · The paper itself

Abstract

Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated.

Indexed as

Basic Helix-Loop-Helix ProteinsCell DifferentiationCells, CulturedChromatin ImmunoprecipitationEnhancer Elements, GeneticGene Expression ProfilingGene Expression Regulation, DevelopmentalGene LibraryHematopoietic Stem CellsHumansMesodermMicroarray AnalysisModels, BiologicalMolecular Sequence DataMyoblasts, CardiacProto-Oncogene ProteinsBasic Helix-Loop-Helix ProteinsProto-Oncogene ProteinsTAL1 protein, humanT-Cell Acute Lymphocytic Leukemia Protein 1cardiac specificationenhancerhematopoiesismesoderm diversificationtranscriptional regulation

Identifiers

PMID25564442
PMCPMC4369313
OpenAlexW2067814074

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.