AP-1 TFs are essential regulators of zebrafish cardiomyocyte regeneration

We show here that AP-1 transcription factor genes are upregulated in border zone cardiomyocytes (CMs) following cryoinjury. Furthermore, using CM-specific dominant-negative approaches, we found that AP-1 contributes to chromatin accessibility changes in regenerating CMs and that AP-1 is essential for multiple aspects of CM regeneration, including dedifferentiation, proliferation, sarcomere disassembly, and invasion of the injured area. Notably, we found that the AP-1 response largely differs in regenerative zebrafish versus nonregenerative mouse CMs and that overexpression of Junb and Fosl1 in mammalian CMs can promote hallmarks of CM regeneration in vitro.

Beisaw A#, Kuenne C, Guenther S, Dallmann J, Wu CC, Bentsen M, Looso M, Stainier DYR#. AP-1 contributes to chromatin accessibility to promote sarcomere disassembly and cardiomyocyte protrusion during zebrafish heart regeneration. Circulation Research. 2020; 126: 1760-1778. #co-corresponding authors

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Cardiomyocyte maturation and its reversal during regeneration