Integration of ATAC- and RNA-sequencing identifies chromatin and transcriptomic signatures in classical and non-classical zebrafish osteoblasts and indicates mechanisms of entpd5a regulation
- 1Institute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, Universität Münster, Münster, Germany
- 2Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, Münster, Germany
- 3Department of Cancer and Genomic Sciences, School of Clinical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom
Abstract
Two types of osteoblasts are required to assemble the zebrafish embryonic skeleton: classical osteoblasts homologous to the mammalian cell and notochord sheath cells which serve as non-classical osteoblasts. The gene entpd5a is critically required for ossification via both types of osteoblasts. Despite the indispensability of zebrafish models in vertebrate research, the genetic regulation of bone formation, as well as mechanisms of transcriptional control of entpd5a, remains largely unknown. Here, using a newly generated transgenic line, we isolate classical and non-classical osteoblasts from zebrafish embryos and performed both assay for transposase-accessible chromatin (ATAC)-seq and RNA-seq. We analysed results independently and integratively to understand those chromatin dynamics and accompanying transcriptomic changes that occur in different skeletal cell types. We show that although Dlx family factors are playing important roles in classical osteoblast regulation, Hox family factors are involved in governing spinal ossification via non-classical osteoblasts. We further present a resource-driven analysis of the entpd5a promoter, experimentally validating the ATAC-seq dataset and proposing mechanisms of regulating the complex entpd5a expression pattern during zebrafish osteogenesis. Our results thus provide a necessary comprehensive resource for the field of bone development and indicate spatio-temporally regulated promoter/enhancer interactions taking place in the entpd5a locus.
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BibTeX
@article{petratou2026integration,
title = {{Integration of ATAC- and RNA-sequencing identifies chromatin and transcriptomic signatures in classical and non-classical zebrafish osteoblasts and indicates mechanisms of entpd5a regulation}},
author = {Kleio Petratou and Martin Stehling and Ferenc Müller and Stefan Schulte-Merker},
journal = {eLife},
year = {2026},
month = oct,
doi = {10.7554/elife.100230},
url = {https://elifesciences.org/articles/100230},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integration of ATAC- and RNA-sequencing identifies chromatin and transcriptomic signatures in classical and non-classical zebrafish osteoblasts and indicates mechanisms of entpd5a regulation
AU - Kleio Petratou
AU - Martin Stehling
AU - Ferenc Müller
AU - Stefan Schulte-Merker
PY - 2026
DA - 2026/10/27
JO - eLife
DO - 10.7554/elife.100230
UR - https://elifesciences.org/articles/100230
AB - Two types of osteoblasts are required to assemble the zebrafish embryonic skeleton: classical osteoblasts homologous to the mammalian cell and notochord sheath cells which serve as non-classical osteoblasts. The gene entpd5a is critically required for ossification via both types of osteoblasts. Despite the indispensability of zebrafish models in vertebrate research, the genetic regulation of bone formation, as well as mechanisms of transcriptional control of entpd5a, remains largely unknown. Here, using a newly generated transgenic line, we isolate classical and non-classical osteoblasts from zebrafish embryos and performed both assay for transposase-accessible chromatin (ATAC)-seq and RNA-seq. We analysed results independently and integratively to understand those chromatin dynamics and accompanying transcriptomic changes that occur in different skeletal cell types. We show that although Dlx family factors are playing important roles in classical osteoblast regulation, Hox family factors are involved in governing spinal ossification via non-classical osteoblasts. We further present a resource-driven analysis of the entpd5a promoter, experimentally validating the ATAC-seq dataset and proposing mechanisms of regulating the complex entpd5a expression pattern during zebrafish osteogenesis. Our results thus provide a necessary comprehensive resource for the field of bone development and indicate spatio-temporally regulated promoter/enhancer interactions taking place in the entpd5a locus.
SN - 2050-084X
ER -