HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration

S. Randal Voss, Larissa V. Ponomareva, Varun B. Dwaraka, Kaitlin E. Pardue, Nour W.Al Haj Baddar, A. Katherine Rodgers, M. Ryan Woodcock, Qingchao Qiu, Anne Crowner, Dana Blichmann, Shivam Khatri, Jon S. Thorson

Research output: Contribution to journalArticlepeer-review

15 Citations (SciVal)

Abstract

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited regeneration through the first 7 days, however after this time, regeneration commenced with variable outgrowth of tailfin tissue and abnormal patterning. Microarray analysis showed that romidepsin altered early, transcriptional responses at 3 and 6-hour post-amputation, especially targeting genes that are implicated in tumor cell death, as well as genes that function in the regulation of transcription, cell differentiation, cell proliferation, pattern specification, and tissue morphogenesis. Our results show that HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration.

Original languageEnglish
Article number6751
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
This research was funded by the National Institutes of Health through their support of this project (R24OD21479) and Ambystoma Genetic Stock Center (P40OD019794).

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration'. Together they form a unique fingerprint.

Cite this