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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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Title:Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos
Creators Name:McGarvey, A.C. and Kopp, W. and Vučićević, D. and Kempfer, R. and Mattonet, K. and Hirsekorn, A. and Bilić, I. and Trinks, A. and Merks, A.M. and Panáková, D. and Pombo, A. and Akalin, A. and Junker, J.P. and Stainier, D.Y.R. and Garfield, D. and Ohler, U. and Lacadie, S.A.
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.
Keywords:Animals, Zebrafish
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.06.26.173377
Date:26 June 2020
Official Publication:https://doi.org/10.1101/2020.06.26.173377

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