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Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos

View ORCID ProfileAlison C. McGarvey, View ORCID ProfileWolfgang Kopp, View ORCID ProfileDubravka Vučićević, View ORCID ProfileRieke Kempfer, View ORCID ProfileKenny Mattonet, Antje Hirsekorn, View ORCID ProfileIlija Bilić, Alexandra Trinks, View ORCID ProfileAnne Margarete Merks, View ORCID ProfileDaniela Panáková, View ORCID ProfileAna Pombo, View ORCID ProfileAltuna Akalin, View ORCID ProfileJan Philipp Junker, View ORCID ProfileDidier Y.R. Stainier, View ORCID ProfileDavid Garfield, View ORCID ProfileUwe Ohler, View ORCID ProfileScott Allen Lacadie
doi: https://doi.org/10.1101/2020.06.26.173377
Alison C. McGarvey
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
2Quantitative Developmental Biology, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
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Wolfgang Kopp
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
3Bioinformatics and Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
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Dubravka Vučićević
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
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Rieke Kempfer
4Epigenetic Regulation and Chromatin Architecture, Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Institute for Biology, Humboldt Universität Berlin, Berlin, Germany
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Kenny Mattonet
5Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
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Antje Hirsekorn
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
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Ilija Bilić
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
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Alexandra Trinks
6IRI Life Sciences, Humboldt Universität Berlin, Berlin, Germany
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Anne Margarete Merks
7Electrochemical Signaling in Development and Disease, Max Delbrück Centre for Molecular Medicine, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
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Daniela Panáková
7Electrochemical Signaling in Development and Disease, Max Delbrück Centre for Molecular Medicine, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
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Ana Pombo
4Epigenetic Regulation and Chromatin Architecture, Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Institute for Biology, Humboldt Universität Berlin, Berlin, Germany
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Altuna Akalin
3Bioinformatics and Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
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  • ORCID record for Altuna Akalin
Jan Philipp Junker
2Quantitative Developmental Biology, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
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Didier Y.R. Stainier
5Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
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David Garfield
8Bayer Pharma AG, Berlin, Germany
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Uwe Ohler
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
9Department of Biology, Humboldt Universität Berlin, Berlin, Germany
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  • For correspondence: scott.lacadie@mdc-berlin.de uwe.ohler@mdc-berlin.de
Scott Allen Lacadie
1Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany
10Berlin Institute of Health, Berlin, Germany
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  • For correspondence: scott.lacadie@mdc-berlin.de uwe.ohler@mdc-berlin.de
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Abstract

DNA accessibility of cis regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many of the genes that regulate embryonic development have been described, the underlying CRE dynamics controlling their expression remain largely unknown. To address this, we applied single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq) to whole 24 hours post fertilization (hpf) stage zebrafish embryos and developed a new computational tool, ScregSeg, that selects informative genome segments and classifies complex accessibility dynamics. We integrated the ScregSeg output with bulk measurements for histone post-translational modifications and 3D genome organization, expanding knowledge of regulatory principles between chromatin modalities. Sci-ATAC-seq profiling of npas4l/cloche mutant embryos revealed novel cellular roles for this hemato-vascular transcriptional master regulator and suggests an intricate mechanism regulating its expression. Our work constitutes a valuable resource for future studies in developmental, molecular, and computational biology.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 26, 2020.
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Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos
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Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos
Alison C. McGarvey, Wolfgang Kopp, Dubravka Vučićević, Rieke Kempfer, Kenny Mattonet, Antje Hirsekorn, Ilija Bilić, Alexandra Trinks, Anne Margarete Merks, Daniela Panáková, Ana Pombo, Altuna Akalin, Jan Philipp Junker, Didier Y.R. Stainier, David Garfield, Uwe Ohler, Scott Allen Lacadie
bioRxiv 2020.06.26.173377; doi: https://doi.org/10.1101/2020.06.26.173377
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Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos
Alison C. McGarvey, Wolfgang Kopp, Dubravka Vučićević, Rieke Kempfer, Kenny Mattonet, Antje Hirsekorn, Ilija Bilić, Alexandra Trinks, Anne Margarete Merks, Daniela Panáková, Ana Pombo, Altuna Akalin, Jan Philipp Junker, Didier Y.R. Stainier, David Garfield, Uwe Ohler, Scott Allen Lacadie
bioRxiv 2020.06.26.173377; doi: https://doi.org/10.1101/2020.06.26.173377

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