Single-cell profiling of transcriptome and histone modifications with EpiDamID

Franka J Rang, Kim L de Luca, Sandra S de Vries, Christian Valdes-Quezada, Ellen Boele, Phong D Nguyen, Isabel Guerreiro, Yuko Sato, Hiroshi Kimura, Jeroen Bakkers, Jop Kind

Research output: Contribution to journal/periodicalArticleScientificpeer-review

19 Citations (Scopus)

Abstract

Recent advances in single-cell sequencing technologies have enabled simultaneous measurement of multiple cellular modalities, but the combined detection of histone post-translational modifications and transcription at single-cell resolution has remained limited. Here, we introduce EpiDamID, an experimental approach to target a diverse set of chromatin types by leveraging the binding specificities of single-chain variable fragment antibodies, engineered chromatin reader domains, and endogenous chromatin-binding proteins. Using these, we render the DamID technology compatible with the genome-wide identification of histone post-translational modifications. Importantly, this includes the possibility to jointly measure chromatin marks and transcription at the single-cell level. We use EpiDamID to profile single-cell Polycomb occupancy in mouse embryoid bodies and provide evidence for hierarchical gene regulatory networks. In addition, we map H3K9me3 in early zebrafish embryogenesis, and detect striking heterochromatic regions specific to notochord. Overall, EpiDamID is a new addition to a vast toolbox to study chromatin states during dynamic cellular processes.

Original languageEnglish
Pages (from-to)1956-1970.e14
JournalMolecular Cell
Volume82
Issue number10
DOIs
Publication statusPublished - 19 May 2022

Keywords

  • Animals
  • Chromatin/genetics
  • Histone Code
  • Histones/genetics
  • Mice
  • Protein Processing, Post-Translational
  • Transcriptome
  • Zebrafish/genetics

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