Evidence map›Paper›PMID 34290256›Full record

ArticleNature communications2021

Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation.

Nathan J VanDusen, Julianna Y Lee, Weiliang Gu, Catalina E Butler, Isha Sethi, Yanjiang Zheng, Justin S King, Pingzhu Zhou, Shengbao Suo, Yuxuan Guo and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

50 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026
    Review
  5. CRISPR and the Future of Cardiac Disease Therapy: A New Genetic Frontier.International journal of molecular sciences · 2026
    Review
  6. Review
  7. Article
  8. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
  9. Decoding RNF20: an epigenetic modifier and beyond.Frontiers in cell and developmental biology · 2026
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Nathan J VanDusenDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2636-7228
Julianna Y LeeDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Weiliang GuDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Catalina E ButlerDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0096-0197
Isha SethiDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Yanjiang ZhengDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Justin S KingDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6469-9872
Pingzhu ZhouDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Shengbao SuoDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Yuxuan GuoDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6009-4403
Qing MaDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Guo-Cheng YuanDepartment of Genetics and Genomic Sciences and Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
William T PuDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA. william.pu@cardio.chboston.org.
Boston Children's Hospital · USDana-Farber Cancer Institute · USIcahn School of Medicine at Mount Sinai · US

Funding

RESEARCH METHODS IN PEDIATRICS HEART DISEASET32HL007572 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Sarah D DE FERRANTI, Jane W. Newburger · 1985 to 2026
$13.0M
Regulation of Cardiac Development in Health and DiseaseUM1HL098166 · NHLBI · HARVARD MEDICAL SCHOOL · PI PENNACCHIO, LEN ALEXANDER, PU, WILLIAM TSWENCHING · 2015 to 2019
$4.4M
A systems biology approach for dissecting enhancer hierarchyR01HG009663 · NHGRI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI YUAN, GUO-CHENG · 2017 to 2020
$2.8M
Regulation of Cardiomyocyte MaturationR01HL146634 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI PU, WILLIAM TSWENCHING · 2019 to 2022
$2.4M
Big Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0M
Functional dissection of the regulatory network that governs cardiomyocyte maturation.K99HL143194 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI VANDUSEN, NATHAN JAMES · 2019 to 2021
$232k
Identification and analysis of factors that regulate cardiomyocyte maturationF32HL134235 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI VANDUSEN, NATHAN JAMES · 2016 to 2017
$73k
NHGRI NIH HHS R01 HG009663NHLBI NIH HHS F32 HL134235NHLBI NIH HHS K99 HL143194NHLBI NIH HHS R01 HL146634NHLBI NIH HHS T32 HL007572NHLBI NIH HHS UM1 HL098166NIH HHS S10 OD026880
6 · The paper itself

Abstract

The forward genetic screen is a powerful, unbiased method to gain insights into biological processes, yet this approach has infrequently been used in vivo in mammals because of high resource demands. Here, we use in vivo somatic Cas9 mutagenesis to perform an in vivo forward genetic screen in mice to identify regulators of cardiomyocyte (CM) maturation, the coordinated changes in phenotype and gene expression that occur in neonatal CMs. We discover and validate a number of transcriptional regulators of this process. Among these are RNF20 and RNF40, which form a complex that monoubiquitinates H2B on lysine 120. Mechanistic studies indicate that this epigenetic mark controls dynamic changes in gene expression required for CM maturation. These insights into CM maturation will inform efforts in cardiac regenerative medicine. More broadly, our approach will enable unbiased forward genetics across mammalian organ systems.

Indexed as

Epigenesis, GeneticAnimalsAnimals, NewbornCRISPR-Cas SystemsGene Expression Regulation, DevelopmentalHistonesMiceMutagenesisMyocytes, CardiacPhenotypeReproducibility of ResultsUbiquitinationUbiquitin-Protein LigasesHistonesRNF20 protein, mouseRnf40 protein, mouseUbiquitin-Protein Ligases

Identifiers

PMID34290256
PMCPMC8295283
OpenAlexW3186400718

What OpenQuestion holds

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Registered trials

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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.