Enhancer selection dictates gene expression responses in remote organs during tissue regeneration

doi:10.1038/s41556-022-00906-y

Enhancer selection dictates gene expression responses in remote organs during tissue regeneration

2022-05-05

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DOI：10.1038/s41556-022-00906-y

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Acute trauma stimulates local repair mechanisms but can also impact structures distant from the injury, for example through the activity of circulating factors. To study the responses of remote tissues during tissue regeneration, we profiled transcriptomes of zebrafish brains after experimental cardiac damage. We found that the transcription factor gene cebpd was upregulated remotely in brain ependymal cells as well as kidney tubular cells, in addition to its local induction in epicardial cells. cebpd mutations altered both local and distant cardiac injury responses, altering the cycling of epicardial cells as well as exchange between distant fluid compartments. Genome-wide profiling and transgenesis identified a hormone-responsive enhancer near cebpd that exists in a permissive state, enabling rapid gene expression in heart, brain and kidney after cardiac injury. Deletion of this sequence selectively abolished cebpd induction in remote tissues and disrupted fluid regulation after injury, without affecting its local cardiac expression response. Our findings suggest a model to broaden gene function during regeneration in which enhancer regulatory elements define short- and long-range expression responses to injury. Sun et al. report that a steroid-responsive enhancer is preferentially required for expression and function of cebpd in remote tissues during heart regeneration.

Keywords:

BINDING-PROTEIN DELTA

HEART REGENERATION

STEM-CELLS

ZEBRAFISH

PROGESTERONE

CAPACITY

FAILURE

GROWTH

ACTIVATION

TRANSITION

Enhancer selection dictates gene expression responses in remote organs during tissue regeneration

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