@article{2507f54fd5ed418c89a93482c242954d,
title = "Single-cell profiling of transcriptome and histone modifications with EpiDamID",
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.",
keywords = "Animals, Chromatin/genetics, Histone Code, Histones/genetics, Mice, Protein Processing, Post-Translational, Transcriptome, Zebrafish/genetics",
author = "Rang, {Franka J.} and {de Luca}, {Kim L.} and {de Vries}, {Sandra S.} and Christian Valdes-Quezada and Ellen Boele and Nguyen, {Phong D.} and Isabel Guerreiro and Yuko Sato and Hiroshi Kimura and Jeroen Bakkers and Jop Kind",
note = "Funding Information: We would like to thank the members of the Kind laboratory for their helpful comments and suggestions. In particular, we thank Koos Rooijers for providing input and support on the computational work. This work was funded by an ERC Starting grant ( ERC-StG 678423-EpiID ) to J.K. The Oncode Institute is partially funded by the KWF Dutch Cancer Society. I.G. is supported by an EMBO Long-Term Fellowship ALTF1214-2016 , Swiss National Science Fund grant P400PB_186758 and NWO-ENW Veni grant VI.Veni.202.073 . P.D.N. is supported by an EMBO Long-Term Fellowship ALTF1129-2015 , HFSPO Fellowship ( LT001404/2017-L ) and an NWO-ZonMW Veni grant ( 016.186.017-3 ). The laboratory of J.B. is supported by the Netherlands Cardiovascular Research Initiative , an initiative with support of the Dutch Heart Foundation and Hartekind , CVON2019-002 OUTREACH . The laboratory of H.K. is supported by MEXT/JSPS KAKENHI ( JP18H05527 , JP20K06484 , and JP21H04764 ) and Japan Science and Technology Agency ( JPMJCR16G1 and JPMJCR20S6 ). We additionally thank the Hubrecht Sorting Facility, the Hubrecht Imaging Center, and the Utrecht Sequencing Facility (USEQ), subsidized by the University Medical Center Utrecht. Funding Information: We would like to thank the members of the Kind laboratory for their helpful comments and suggestions. In particular, we thank Koos Rooijers for providing input and support on the computational work. This work was funded by an ERC Starting grant (ERC-StG 678423-EpiID) to J.K. The Oncode Institute is partially funded by the KWF Dutch Cancer Society. I.G. is supported by an EMBO Long-Term Fellowship ALTF1214-2016, Swiss National Science Fund grant P400PB_186758 and NWO-ENW Veni grant VI.Veni.202.073. P.D.N. is supported by an EMBO Long-Term Fellowship ALTF1129-2015, HFSPO Fellowship (LT001404/2017-L) and an NWO-ZonMW Veni grant (016.186.017-3). The laboratory of J.B. is supported by the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation and Hartekind, CVON2019-002 OUTREACH. The laboratory of H.K. is supported by MEXT/JSPS KAKENHI (JP18H05527, JP20K06484, and JP21H04764) and Japan Science and Technology Agency (JPMJCR16G1 and JPMJCR20S6). We additionally thank the Hubrecht Sorting Facility, the Hubrecht Imaging Center, and the Utrecht Sequencing Facility (USEQ), subsidized by the University Medical Center Utrecht. Conceptualization: F.J.R. K.L.d.L. S.S.d.V. and J.K. Data curation & Validation: F.J.R. K.L.d.L. and S.S.d.V. Formal analysis & Software: F.J.R. Funding acquisition & Project administration: J.K. Investigation & Methodology: K.L.d.L. and S.S.d.V. designed and performed all experiments unless noted otherwise. C.V.Q. and E.B. designed and generated knock-in mouse ESC lines. P.D.N. performed all zebrafish experiments, with assistance from I.G. and S.S.d.V. Resources: Y.S. and H.K. Supervision: J.B. and J.K. Visualization: F.J.R. and K.L.d.L. Writing – original draft: F.J.R. K.L.d.L. and J.K. Writing – review & editing: all authors. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = may,
day = "19",
doi = "10.1016/j.molcel.2022.03.009",
language = "English",
volume = "82",
pages = "1956--1970.e14",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "10",
}