Decoding an organ regeneration switch by dissecting cardiac regeneration enhancers.

Autor:	Begeman IJ; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA., Shin K; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA., Osorio-Méndez D; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA., Kurth A; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA., Lee N; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA., Chamberlain TJ; Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53705, USA., Pelegri FJ; Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53705, USA., Kang J; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.; UW Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2020 Dec 23; Vol. 147 (24). Date of Electronic Publication: 2020 Dec 23.
DOI:	10.1242/dev.194019
Abstrakt:	Heart regeneration in regeneration-competent organisms can be accomplished through the remodeling of gene expression in response to cardiac injury. This dynamic transcriptional response relies on the activities of tissue regeneration enhancer elements (TREEs); however, the mechanisms underlying TREEs are poorly understood. We dissected a cardiac regeneration enhancer in zebrafish to elucidate the mechanisms governing spatiotemporal gene expression during heart regeneration. Cardiac lepb regeneration enhancer ( cLEN ) exhibits dynamic, regeneration-dependent activity in the heart. We found that multiple injury-activated regulatory elements are distributed throughout the enhancer region. This analysis also revealed that cardiac regeneration enhancers are not only activated by injury, but surprisingly, they are also actively repressed in the absence of injury. Our data identified a short (22 bp) DNA element containing a key repressive element. Comparative analysis across Danio species indicated that the repressive element is conserved in closely related species. The repression mechanism is not operational during embryogenesis and emerges when the heart begins to mature. Incorporating both activation and repression components into the mechanism of tissue regeneration constitutes a new paradigm that might be extrapolated to other regeneration scenarios. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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