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bioRxiv · 10.1101/2023.02.13.528361

Cis-regulatory landscapes of the fat-tailed dunnart and mouse provide insights into the drivers of craniofacial heterochrony

Cook, L. E.·Feigin, C. Y.·Pask, A. J.·Gallego Romero, I.
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Abstract

Marsupials and placental mammals exhibit significant differences in reproductive and life history strategies. Marsupials are born highly underdeveloped after an extremely short period of gestation, leading to prioritization of the development of structures critical for post-birth survival in the pouch. Critically, they must undergo accelerated development of the oro-facial region compared to placentals. Previously we described the accelerated development of the oro-facial region in the carnivorous Australian marsupial, the fat-tailed dunnart Sminthopsis crassicaudata that has one of the shortest gestations of any mammal. By combining genome comparisons of the mouse and dunnart with functional data for the enhancer-associated chromatin modifications, H3K4me3 and H3K27ac, we investigated divergence of craniofacial regulatory landscapes between these species. This is the first description of genome-wide face regulatory elements in a marsupial, with 60,626 putative enhancers and 12,295 putative promoters described. We also generated craniofacial RNA-seq data for the dunnart to investigate expression dynamics of genes near predicted active regulatory elements. While genes involved in regulating facial development were largely conserved in mouse and dunnart, the regulatory landscape varied significantly. Additionally, a subset of dunnart-specific enhancers were associated with genes highly expressed only in dunnart relating to cranial neural crest proliferation, embryonic myogenesis and epidermis development. Comparative RNA-seq analyses of facial tissue revealed dunnart-specific expression of genes involved in the development of the mechanosensory system. Accelerated development of the dunnart sensory system likely relates to the sensory cues received by the nasal-oral region during the postnatal journey to the pouch. Together these data suggest that accelerated face development in the dunnart may be driven by dunnart-specific enhancer activity. Our study highlights the power of marsupial-placental comparative genomics for understanding the role of enhancers in driving temporal shifts in development.

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Cook, L. E., Feigin, C. Y., Pask, A. J., Gallego Romero, I.. 2023-02-14. Cis-regulatory landscapes of the fat-tailed dunnart and mouse provide insights into the drivers of craniofacial heterochrony. https://doi.org/10.1101/2023.02.13.528361

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