Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension

Mok, Gi Fay, Folkes, Leighton, Weldon, Shannon A., Maniou, Eirini, Martinez-Heredia, Victor, Godden, Alice M., Williams, Ruth M., Sauka-Spengler, Tatjana, Wheeler, Grant N., Moxon, Simon and Münsterberg, Andrea E. (2021) Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension. Nature Communications, 12 (1). ISSN 2041-1723

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Abstract

Somites arising from paraxial mesoderm are a hallmark of the segmented vertebrate body plan. They form sequentially during axis extension and generate musculoskeletal cell lineages. How paraxial mesoderm becomes regionalised along the axis and how this correlates with dynamic changes of chromatin accessibility and the transcriptome remains unknown. Here, we report a spatiotemporal series of ATAC-seq and RNA-seq along the chick embryonic axis. Footprint analysis shows differential coverage of binding sites for several key transcription factors, including CDX2, LEF1 and members of HOX clusters. Associating accessible chromatin with nearby expressed genes identifies cis-regulatory elements (CRE) for TCF15 and MEOX1. We determine their spatiotemporal activity and evolutionary conservation in Xenopus and human. Epigenome silencing of endogenous CREs disrupts TCF15 and MEOX1 gene expression and recapitulates phenotypic abnormalities of anterior–posterior axis extension. Our integrated approach allows dissection of paraxial mesoderm regulatory circuits in vivo and has implications for investigating gene regulatory networks.

Item Type: Article
Uncontrolled Keywords: chemistry(all),biochemistry, genetics and molecular biology(all),physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science
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Depositing User: LivePure Connector
Date Deposited: 05 Mar 2021 00:44
Last Modified: 30 Sep 2021 16:16
URI: https://ueaeprints.uea.ac.uk/id/eprint/79378
DOI: 10.1038/s41467-021-21426-7

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