A histone demethylase is necessary for regeneration in zebrafish
- aGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; and
- bCenter of Regenerative Medicine in Barcelona,E-08003 Barcelona, Spain
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Edited by Clifford J. Tabin, Harvard Medical School, Boston, MA, and approved October 1, 2009 (received for review April 15, 2009)
Abstract
Urodele amphibians and teleost fish regenerate amputated body parts via a process called epimorphic regeneration. A hallmark of this phenomenon is the reactivation of silenced developmental regulatory genes that previously functioned during embryonic patterning. We demonstrate that histone modifications silence promoters of numerous genes involved in zebrafish caudal fin regeneration. Silenced developmental regulatory genes contain bivalent me3K4/me3K27 H3 histone modifications created by the concerted action of Polycomb (PcG) and Trithorax histone methyltransferases. During regeneration, this silent, bivalent chromatin is converted to an active state by loss of repressive me3K27 H3 modifications, occurring at numerous genes that appear to function during regeneration. Loss-of-function studies demonstrate a requirement for a me3K27 H3 demethylase during fin regeneration. These results indicate that histone modifications at discreet genomic positions may serve as a crucial regulatory event in the initiation of fin regeneration.
Footnotes
- 1To whom correspondence may be addressed. E-mail: belmonte{at}salk.edu or izpisua{at}cmrb.eu
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Author contributions: S.S. and J.C.I.B. designed research; S.S. and Z.-Y.T. performed research; S.S. and J.C.I.B. analyzed data; and S.S. and J.C.I.B. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0904132106/DCSupplemental.
