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ToolsWeldon, Shannon A., Smith, Emily L., Schatka, Magdalena, Folkes, Leighton, Mok, Gi Fay, Lister, Ashleigh, Macaulay, Iain C., Hearty, Wilfried and Münsterberg, Andrea E. (2025) Transcriptomics and chromatin accessibility signatures define the cervical-thoracic boundary along the vertebrate axis. Developmental Biology, 525. pp. 249-258. ISSN 0012-1606
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Abstract
In vertebrate embryos, somite pairs form on either side of the neural tube along the main body axis. Somites generate the tissues of the musculoskeletal system, including cartilage of the vertebral column and ribs and skeletal muscles of the trunk and limbs. The detailed anatomy of somite-derived tissues varies along the axis, with unique features most easily visible in the vertebral column. Here we investigate the genetic control of this regionalization, which drives the subsequent cell differentiation programmes, focusing on the cervical to thoracic (C-T) boundary. Using ATAC-sequencing and RNA-sequencing, we establish molecular profiles of somites, in particular the chromatin landscapes and transcriptional programmes, that define this anatomical transition. Differential analysis highlights candidate cis-regulatory elements (CRE), and in silico footprints identify coverage of transcription factor (TF) binding sites associated with differentially expressed genes. Electroporation of citrine reporters in vivo validates the activity of CREs associated with key HOX genes, HOXC6 and HOXC8. HOXC6 footprints indicate its role in regulating a trio of differentially expressed SOX transcription factors, SOX5, SOX6 and SOX9, which are involved in chondrogenesis. In addition, the differential analysis identifies several lncRNAs, including one that is located within the HOXC cluster. CRISPR-on experiments suggest HOXC6 regulates its expression and therefore we name it lncRNA-HOXC6TA, however, its function in the thoracic region is currently unknown. Our study provides valuable datasets and illustrates how they can be mined to gain further insights into the regulatory mechanisms underlying the C-T transition along the vertebrate body axis.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability: The data presented in the study are deposited in the European Nucleotide Archive repository, accession number PRJEB79488. (embargoed until acceptance) Funding information: Shannon A. Weldon, Emily L. Smith and Magdalana Schatka were supported by BBSRC NRPDTP studentships. LF and GFM were supported by BBSRC grant BB/N007034/1 to AM. WH, IM, and AL were supported by the BBSRC Core Strategic Programme Grant (BB/CSP1720/1) and its components (BBS/E/T/000PR9818, BBS/E/T/000PR9819, BBS/E/T/000PR9817) and the BBSRC Earlham Institute Strategic Programme Grant Cellular Genomics BBX011070/1 (BBS/E/ER/230001A , BBS/E/ER/230001B , BBS/E/ER/230001C ). IM and AL were supported by the BBSRC Core Capability Grant BB/CCG1720/1 and the National Capability ( BBS/E/T/000PR9816 ). |
| Uncontrolled Keywords: | atac-sequencing,axis development,hox genes,lncrna,rna-sequencing,molecular biology,developmental biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1312 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Science |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 30 Jun 2025 11:30 |
| Last Modified: | 14 Jul 2025 12:32 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99770 |
| DOI: | 10.1016/j.ydbio.2025.06.012 |
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