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A Single-Cell Transcriptomics CRISPR-Activation Screen Identifies Epigenetic Regulators of the Zygotic Genome Activation Program

Authors
  • Alda-Catalinas, Celia1, 2
  • Bredikhin, Danila3
  • Hernando-Herraez, Irene1
  • Santos, Fátima1
  • Kubinyecz, Oana1
  • Eckersley-Maslin, Mélanie A.1
  • Stegle, Oliver3, 4, 5, 2
  • Reik, Wolf1, 2, 6
  • 1 Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK
  • 2 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
  • 3 European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany
  • 4 Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
  • 5 European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SA, UK
  • 6 Centre for Trophoblast Research University of Cambridge, Cambridge CB2 3EG, UK
Type
Published Article
Journal
Cell Systems
Publisher
Cell Press
Publication Date
Jul 22, 2020
Volume
11
Issue
1
Pages
25–41
Identifiers
DOI: 10.1016/j.cels.2020.06.004
PMID: 32634384
PMCID: PMC7383230
Source
PubMed Central
Keywords
License
Unknown

Abstract

Alda-Catalinas et al. developed a pooled CRISPR-activation screen combined with single-cell transcriptomics to identify regulators of zygotic genome activation (ZGA) using an in vitro proxy of early mouse embryos, embryonic stem cells. After interrogation of 230 candidate regulators, 24 hits were identified using multi-omics factor analysis (MOFA+), including the transcription factor Patz1 , the DNA-binding protein Dppa2 , and the chromatin remodeler Smarca5 . Follow-up functional experiments demonstrated that Smarca5’ s regulation of ZGA-like transcription is dependent on Dppa2 .

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